IMIDAZOLE 5-POSITION SUBSTITUTED ANGIOTENSIN II ANTAGONISTS

Abstract: Novel substituted imidazoles of Formula (I), which are useful as angiotensin II antagonists, are disclosed.

Description: TITLE IMIDAZOLE 5-POSITION SUBSTITUTED ANGIOTENSIN II ANTAGONISTS BACKGROUND OF THE INVENTION Field of the Invention This invention relates to novel imidazole 5-position substituted angiotensin II antagonists. The invention also relates to pharmaceutical compositions containing these novel imidazoles and pharmaceutical methods using them, alone and in conjugation with other drugs, especially diuretics, angiotensin converting enzyme (ACE) inhibitors, and non-steroidal anti- inflammatory drugs (NSAIDS). The compounds of this invention inhibit the action of the hormone angiotensin II (All) and are useful therefore in alleviating angiotensin induced hypertension. The enzyme renin acts on a blood plasma a2-globulin, angiotensinogen, to produce angiotensin I, which is then converted by ACE to All. The latter substance is a powerful vasopressor agent which has been implicated as a causative agent for producing high blood pressure in various mammalian species, such as the rat, dog, and man. The compounds of this invention inhibit the action of All at its receptors on target cells and thus prevent the increase in blood pressure produced by this hormone-receptor interaction. By administering a compound of this invention to a species of mammal with hypertension due to All, the blood pressure is reduced. Administration of a compound of this invention with a diuretic such as furosemide or hydrochlorothiazide, either as a stepwise combined therapy (diuretic first) or as a physical mixture, enhances the antihypertensive effect of the compound. Administration of a compound of this invention with a NSAID can prevent renal failure which sometimes results from administration of a NSAID. Several peptide analogs of All are known to inhibit the effects of this hormone by competitively blocking the receptors, but their experimental and clinical applications have been limited by their partial agonist activity and lack of oral absorption (M. Antonaccio, Clin. Exp. Hypertens., 1982, A4, 27-46; D. H. P. Streeten and G. H. Anderson, Jr. - Handbook of Hypertension. Olinical Pharmacology of Antihvpertensive Drugs, ed., A. E. Doyle, Vol. 5, pages 246- 271 , Elsevier Science Publisher, Amsterdam, The Netherlands, 1984). Several non-peptide antagonists of angiotensin II, including some biphenylmethyl imidazoles, have been disclosed. U.S. Patents 5,137,902 and 5,138,069 disclose biphenylmethylimidazoles (A) where R 1 may be a (A) (B) phenyl substituted in the 2'-position with acidic functional groups, such as carboxy and tetrazole, and where imidazole substitutent R 7 may be alkyl or optionally substituted phenyl, and where R^ may be formyl, acyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkoxyalkyl and hydroxyalkyl. U.S. Applications Serial No. 90/03683 and Serial No. 07/545302 disclose substituted imidazoles of the same basic structure where R 7 may be optionally substituted aryl or heteroaryl. European Application EP401 ,030 (Merck) describes imidazoles of structure (B), where Q represents various nitrogenous functional groups, T may be carboxy, alkoxycarbonyl or aminocarbonyl, r may be 1 , (X)q can represent a single bond, R 6 (B)p may represent alkyl and R 1 may be SO2NHR 9 , SO2NH-heteroaryl, SO NHCOR25 or S0 2 NHCONHR 2 5, where R9 is H, alkyl, phenyl or benzyl, and where R 2 ^ is aryl, heteroaryl, cycloalkyl or optionally substituted alkyl. Australian Application AU-A-80163/91 (EP465.368, Roussel-Uclaf) discloses substituted imidazoles (C) where R 1 may be alkyl, m may be 1 , either R 2 or R 3 is OR 4 , or a sulfurous group of structure -S(0) n R 4 , (CH 2 ) m I Y (C) -SO(R 4 )=NS(0) n X' or -SSR 4 , where R 4 represents a variety of optionally substituted alkyl, alkenyl, alkynyl, acyl or nitrogenous or sulfurous radicals. The imidazole nitrogen substituent (CH2)m-Y may represent a biphenylmethyl group, which may be substituted in the 2'-position by acidic groups, such as -(CH2)m1 -S(0)m2-X-R 1 0 . in which ml may be 0-4, m2 may be 0-2, X may be a single bond, -NH-, -NH-CO-, or -NH-CO-NH-and R 0 is an optionally substituted alkyl, alkenyl, aryl or heteroaryl radical. European Application EP479.479 (Merck) discloses biphenylmethyl imidazoles (D) where R 1 B may represent alkyl, R 3 may be H, alkyl, alkenyl or alkynyl, perfluoroalkyl, halogen, -NO2, -CN or optionally substituted phenyl, R 4 includes formyl, acyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkoxyalkyl and hydroxyalkyl, X may be a single bond, and R 5 includes -Sθ2NH-heteroaryl, -SO2NHCOR 1 2 and -Sθ2NHCONR 2 R 12 , in which R 2 is H or alkyl, and R 1 is aryl, heteroaryi, cycloalkyl, perfluoroalkyl or optionally substituted C1 -C4 alkyl, where the alkyl substituents include aryl, heteroaryl, alkyl, OH, SH, alkoxy, thioalkoxy, halo, carboxy, alkoxycarbonyl, -NO2, optionally substituted amino and various phosphoryl radicals. (D) European patent application number EPA 503,162, (published September 16, 1992, Hoechst Aktiengesellschaft) describes compounds of structure (E) wherein Z can be nitrogen, and X and Y are independently CR 2 . R 1 can be alkyl, alkenyl, alkynyl, cycloalkyl, cy αalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, or benzyl. R 2 can be H, halogen, nitro perfluoroalkyl, pentafluorophenyl, cyano, phenyl, phenylalkyl, alkyl, alkenyl, phenylalkenyl, imidazolylalkyl, triazolylalkyl, tetrazolylalkyl, ethers, esters, thioethers, sulfides, sulfoxides, sulfones, amides and other groups as well. L-(0)q-A may represent a biphenylmethyl group which may be substituted in the 2' position with an acidic radical. (E) None of the above publications disclose the imidazole biphenylsulfonyl carbamates of the present invention. It is well known that two types of angiotensin II receptors are widely distributed in various mammalian tissues (P. C. Wong etal., Cardiovascular Drug Reviews 192 ' \ ; 9: 317-339; Trends in Endocrinol. Metab. 1992; 3: 211-217). The angiotensin II receptor most directly involved in the mediation of blood pressure is termed the AT-| receptor, and is characterized by high sensitivity to the non-peptide antagonist DuP 753. A second angiotensin II receptor, designated AT2, is sensitive to another class of non-peptide All antagonists, represented by PD123177 (ibid.), and to the peptide CGP42112A. Angiotensin II has approximately equal affinity for both receptor subtypes. Recent evidence suggests that the AT2 receptor may have a role in mediating the synthesis and breakdown of cardiac connective tissues. For example, Matsubara et DuP 753 PD123177 CGP42112A = nicotinic acid-Tyr-(Na-benzyloxy- carbonyl-Arg)Lys-His-Pro-lle-OH al. (The FASEB Journal 6, 4: A941 , 1992) have reported that PD123177, but not DuP 753, blocks the All-stimulated inhibition of collagenase in cultured cardiac fibroblasts. Both PD123177 and DuP 753 are reported by Zhou et al. to block the All-stimulated increase in collagen synthesis in cardiac fibroblasts {The FASEB Journal 6, 4: A1914, 1992). Tsutsumi and Saavedra have found AT2 receptors in cerebral arteries (Am. J. Physiol. 261: H667-H670, 1991 ). An analog of PD123177, PD123319, has been reported by Brix and Haberl (The FASEB Journal 6, 4: A1264, 1992) to block the p : al artery dilation induced by angiotensin II in a rat cranial window preparation monitored by intravital microscopy. This suggests that the AT2 receptor may have a role in modifying cerebral blood flow. The AT2 selective antagonist CGP42112A has been reported by LeNoble et al. (The FASEB Journal 6, 4: A937, 1992) to block the increase in microvascular density induced by angiotensin II in the chick chorioallantoic membrane, suggesting that angiotensin II may in some contexts mediate angiogenesis through AT2 receptors. As noted above, DuP 753, disclosed in U. S. Patent 5,138,069, is a selective AT-| antagonist, having extremely low affinity for the AT2 receptor. No data is presented in U. S. Patent 5,138,069 or the other references above which suggests that any of the compounds disclosed possess high AT2 affinity. In addition to potent AT-| antagonist and antihvpertensive properties, the imidazole compounds of the present invention possess potent AT2 antagonist properties. Since AT1 antagonism leads to increased levels of circulating angiotensin II in vivo (Y. Christen et al., Am. J. Hypertension, 1991 ; 4: 350S-353S), and the AT2-mediated consequences, if any, of higher All levels are unknown, simultaneous AT1 /AT2 antagonism may prove desirable during AT1 -targeted therapy. Summary of the Invention This invention pertains to novel angiotensin II blocking imidazole compounds of the following Formula (I): (w) N-N H , H , (y) N-N 4 ^ N ^CF 3 H (cc) (ii) -SO2NHCO2R 10 ; s independently (a) H, (c) phenyl, or phenyl optionally substituted with halogen (F, CI, Br, I), C1-C4-alkyl, -OH, C1-C4-alkoxy, -N0 2 , -NR 2 6R2 , -NR26C0R 11 , -NR26C0 2 R 7 , -S(0) r R 10 , -S02NR 2 6R27 ( -NR 6SO2R 10 , -CF 3 , (c) Cι -C4-perfluoroalkyl, (d) Ci -C4-alkyl, optionally substituted with a substituent selected from the group consisting of aryl, heteroaryl , -OH, -SH, Cι-C4-alkyl, Cv C4-alkoxy, Ci -C4-alky!thio, -CF3, halo, -NO2, -CO2R 12 , -NH2, C1 -C4- alkylamino, Ci -C4-dialkylamino, -PO3H2, or (e) heteroaryl; R 1 1 , R 1 1a and R 11 b are independently (c) -CH2CH=CH2, or (d) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, Cι-C4-alkyl, Ci- C4-alkoxyor-Nθ2; Rl5is (a) H, (b) Ci-Cβ-alkyl, (c) Ci-Cβ-perfluoroalkyI, (d) C3-C6-cycloalkyl, (e) aryl, or (f) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, Cι-C4-alkyl, Ci- C4-alkoxyor-N02; Rl6is (a) H, (b) Cι-C6-alkyl, or (c) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, Cι-C4-alkyl, Cv C4-alkoxy or-N02; Rl7is (a) H, (b) Cι-C6-alkyl, (c) C3-C6-cycloalkyl, (d) aryl, or (e) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, Cι-C4-alkyl, Ci- C4-alkoxyor-N02; R18 is (a) -NR 1 9R 0, (b) -NHCONH2, (c) -NHCSNH2, or (d) -NHSO2-C6H5; R19 and R20 are independently (a) H, (b) Cι-C5-alkyl, or (c) aryl, R21 and R22 are independently (a) Ci -C4-alkyl, or taken together are (b) -(CH 2 )q-; R23 and R 24 are, independently (a) H, (b) Ci-Cβ-alkyl, (c) aryl, or (d) -(Cι-C4-alkyl)-aryl, or (e) R 3 and R 24 when taken together constitute a pyrrolidine, piperidine or morpholine ring; (a) H, (b) Cι -C6-alkyl, (c) aryl, (d) -(Cι-C4-alkyl)-aryl, (e) C3-C6-alkenyl, or (f) -(C3-C6-alkenyl)-aryl; R26 an d R27 are independently (a) H, (b) Cι -C4-alkyl, (c) aryl, or (d) -CH 2 -aryl; p28 is (a) aryl, or (b) heteroaryl; R2 9 is (a) -CHO, (b) -CONH2, (c) -NHCHO, (d) -CO-(Cι-C6 perfluoroalkyl), (e) -S(0)r(Cι-C6 perfluoroalkyl), (f) -0-(Cι-C6 perfluoroalkyl), or (g) -NRl1 .(c.|-C6 perfluoroalkyl); (a) -CHO, (b) -S0 2 -(Cι-C6 perfluoroalkyl), or (c) -CO-(Cι-C6 perfluoroalkyl); A is (a) -(CH 2 )n-L 1 -B-(T)y-(B)y-X 2 -(B)y-R28, (b) -(CH2)n-L 1 -B-T-(B) y -R28, (c) -(CH2)n-L 1 -B-(T)y-(B) y -X 2 -B, (d) -(CH )n-L 1 -B-T-(B)y-R 2 9, (e) -(CH2)n-L 1 -T-(B)y-X 2 -(B)y-R28, (f) -(CH 2 )n-Ll-T-(B)y-R28, (g) -(CH 2 )n-L 1 -T-(B)y-X2-B, (h) -(CH2)n-L 1 -(CR 1 9R20)-D-(T)y-(B)y-X3-(B) y -R28, 0) -(CH2)n-L 1 -(CR 1 9R20)-D-T-(B)y-R28, G) -(CH2)n-L 1 -(CR 1 9R20)-D-(T)y-(B)y-X3-B, (k) -(CH2)n-L 1 -(CR 1 9R20)-D-T-(B) y -R 9, (I) -(CH2)n-L 1 -(CR 19 R20)-D-T-(B)y-X 4 -(B)y-R28 , (m) -(CH2)n-L 1 -(CR 1 9R20)-D-B-X 4 -(B) y -R 8 , (n) -(CH2)n-L 1 -(CR 1 9R20)-D-T-(B)y-X -B, (o) -(CH2)n-L 1 -(CR 1 9R20)-D-B-X 4 -B, (P) -(CH2)n-L 2 -B-(T)y-(B) y -X 2 -(B) y -R28, (q) -(CH 2 )n-L 2 -B-T-(B)y-R28, (r) -(CH 2 )n-L 2 -B-(T)y-(B) y -X -B, (s) -(CH2)n-L 2 -B-T-(B) y -R 2 9, (t) -(CH 2 )n-L -T-(B) y -X 2 -(B)y-R28, (u) -(CH 2 )n-L 2 -T-(B) y -R28, (v) -(CH2)n-L 2 -T-(B)y-X 2 -B. (w) -(CH2)n-L -D-(T)y-(B)y-X3-(B)y-R28, (x) -(CH2)n-L 2 -D-T-(B) y -R28, (y) -(CH2)n-L -D-(T)y-(B)y-X3-B, W -(CH2)n-L 2 -D-T-(B) y -R 2 9, (aa) -(CH2)n-L 2 -D-T-(B) y -X 4 -(B)y-R28 (bb) -(CH2)n-L -D-B-X 4 -(B)y-R28, (cc) -(CH )n-L 2 -D-T-(B)y-X 4 -B, (dd) -(CH2)n-L 2 -D-B-X -B, (ee) -(CH2)m-L3-B-(T)y-(B)y-X -(B) y -R28, (« -(CH2)m-L3-B-T-(B) y -R28, (gg) -(CH2)m-L3-B-(T)y-(B) y -X 2 -B, (hh) -(CH )m-L3-B-T-(B)y-R 2 9, (ϋ) -(CH 2 )m-L3-T-(B)y-X 2 -(B)y-R28 > GJ) -(CH2)m-L3-T-(B) y -R28, (kk) -(CH2)m-L3-T-(B) y -X 2 -B, (II) -(CH2)m-L3-(CRl9R20)-D-(T)y-(B)y-X3-(B)y-R28, (mm) -(CH2)m-L 3 -(CR' | 9R20).D-T-(B)y-R28 ) (nn) -(CH2)m-L3-(CR 1 9R20)-D-(T)y-(B) y -χ3-B, (oo) -(CH2)m-L3-(CR 1 9R20)-D-T-(B) y -R 2 9, (PP) -(CH2)m-L 3 -(CR 9R20)-D-T-(B)y-X4-(B)y-R28, (qq) -(CH2)m-L 3 -(CR 9R20)-D-(B)-X 4 -(B)y-R28, (rr) -(CH2)m-L 3 -(CRi9R20)_. D -T-(B)y-X -B, (ss) -(CH2)m-L 3 -(CR 1 9R20)-D-B-X 4 -B, (tt) (uu) R 30 (ww) R 30 (xx) -(CH 2 ) n -L 1 -(CR 19 R 20 )-D — ' (CH 2 ) k (yy) R 30 -(CH 2 ) n -L 1 -(CR 19 R 2 VD- : (zz) X*(B) y -R 2 -(CH 2 ) n -L 22 --DD — \_ (C 'H 2 ) k /k (aaa) >30 (bbb) χ5(B) v -R 28 Υ -(CH 2 ) m -L 3 -(CR 1 2 ) k .or (ccc) R 30 L " ! is (a) -C02-, (b) -CONR 11 a-, (c) -NR 11a Cθ2-, or (d) -NR 1 1acONR 1 1b-; L 2 is (a) -CO-, (c) -O2C-; L3is (a) -0-, (b) -SO-, or . (c) -NRl1a. ; B is C1-C6 alkyl; D is C2-C8 alkenyl or C2-C8 alkynyl; Tis (e) -(CH2)n-L 2 -B-(T)y-(B) y -X 2 -(B)y-R28, (f) -(CH2)n-L 2 -B-T-(B)y-R28, or (g) -(CH2)n-L2-B-(T) y -(B) y -X 2 -B, (h) -(CH2)n-L -B-T-(B) y -R 9; One embodiment of the preferred invention above is a compound of formula II R6 j IS from the group consisting of aryl, heteroaryl, -OH, -SH, Ci -C4-alkyl, Ci ■ C4-alkoxy, Cι-C4-alkylthio, -CF3, halo, -NO2, -CO2R 1 2 , -NH2, C1-C4- alkylamino, Ci -C4-dialkylamino, -PO3H2, or (e) heteroaryl; R 1 , R 1 1 a and R 1 1 b are independently substituents selected from the group consisting of halo, Cι-C4-alkyl, Ci- C4-alkoxyor-N02; R 28 is (d) Ci -C4-alkyl, optionally substituted with a substituent selected from the group consisting of aryl, heteroaryl, -OH, -SH, Cι -C4-alkyl, Cv C4-3lkoxy, Cι-C4-3lkylthio, -CF3, halo, -NO2, -CO2R 1 , -NH2, C1-C4- alkylamino, Cι-C4-dialkylamino, -PO3H2, or (e) heteroaryl; R1 1 , R 1 1 a and R 1 1 b are independently (c) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, Cι-C4-alkyl, Ci C4-alkoxy or -Nθ2; R 28 is (m) -OCONR113S02-, (n) -S02NRl l 3C0NRl 1 b. f (o) -NRl l3C0NRl 1 bS02-. (q) -CONRl l3Sθ2NR 1b. t 0 r and pharmaceutically acceptable salts of these compounds. Illustrative of the preferred compounds .of the invention are the following: 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-benzoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H-imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-5-[2-(N-benzoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1 -((2'-((n-Propyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-5-[2-(N-benzoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4- yl)methyl)-5-[2-(N-benzoyl-N-butylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4- yl)methyl)-5-[2-(N-benzoyl-N-propylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1 -((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 , 1 '-biphenyl)-4- yl)methyl)-5-[2-(N-butyryl-N-propylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-5-[2-(N-butyryl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-butyryl-N-phenylamino)ethylcarbonyl]-4-ethyI-2-propyl-1 H-imidazole 1-((2 * -((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-isonicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4- yl)methyl)-5-[2-(N-isonicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2- propyl-1 H-imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1,1'-biphenyl)-4- yl)methyl)-5-[2-(N-nicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2- propyl-1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-nicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2 , -((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-nicotinoyl-N-pyridin-2-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-isonicotinoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-butyryl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1 -((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4-yl)methyl)- 5-[2-(N-isobutyryl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-5-[2-(N-acetyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl- 1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl)- 5-[2-(N-butyryl-N-pyridin-2-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1 -((2'-((i-Amyloxycarbonylamino)sulfonyI)-(1 ,1 '-biphenyl)-4-yl)methyl)-5-[2-(N- butyryl-N-pyridin-3-ylamino)ethylcarbonyl]-2-butyl-4-chloro-1 H-imidazole 1 -((2'-((i-amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4-yl)methyl)- 5-[2-(N-propionyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H- imidazole 1 -((2'-((i-Amyloxycarbonylamino)sulfonyl)(1 ,1 '-biphenyl)-4-yl)methyl)-5-[2-(N- nicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H-imidazole 1-((2 , -((i-Amyloxycarbonylamino)sulfonyl)(1 ,1 , -biphenyl)-4-yl)methyl)-5-[2-(N- butyryl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H-imidazole 1 -((2'-((n-Butyloxycarbonyl-amino)sulfonyl)-3-fluoro-(1 , 1 '-biphenyl)-4- yl)methyl)-4-ethyl-5-(2-(2-phenoxyphenyl)ethylcarbonyl)-2-propyl-1H- imidazole 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethylr2-n-propyl)imidazol-1-yl)methyl]- 3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 3-fluoro-2'-((2-phenyl)ethyloxycarbonylaminosulfonyl)-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 2'-((2-phenyl)ethyloxycarbonylaminosulfonyl)-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 3-fluoro-2'-n-isoamyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 2'-n-isoamyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 3-fluoro-2'-n-propyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-lsoamyloxybenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1- yl)methyl]-3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Phenylaminocarbonyl)benzyloxycarbonyl-4-ethyl-2-n- propyl)imidazol-1 -yl)methyl]-3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 , 1 '- biphenyl. 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl]- 3-fluoro-2'-(1 H-tetrazol-5-yl)-1 ,1 '-biphenyl 4-[((5-)2-trifluorophenyl)methylaminocarbonyl)-4-ethyl-2-n-propyl)imidazol-1 - yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl N-butyl, N-benzyl-2-(aminocarbonyl)ethynylmethyl 4-ethyl-2-propyl-1-[[2'-(1 H- tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N, N-diphenyl-2-(aminocarbonyl)ethynylmethyl 4-ethyl-2-propyl-1-[[2'-(1 H- tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N-phenyl-2-(aminocarbonyl)ethyl 4-ethyl-2-propyl-1 -[[2'-(1 H-tetrazol-5- yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N-butyl, N-benzyl-4-(aminocarbonyl)propyl 4-ethyl-2-propyl-1-[[2'-(1H-tetrazol- 5-yl)biphenyl-4-yl]methyl]imidazole-5-carbox ' ylate N, N-dipentyl-4-(aminocarbonyl)propyl 4-ethyl-2-propyl-1 -[[2'-(tetrazol-5- yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate 4-[(5-((2-benzoyl)phenylcarbonyloxymethyl)-4-chloro-2-n-propylimidazol-1- yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonylbiphenyl 1 -((2'-((n-butyloxycarbonylamino)sulfonyl)-3-f luoro-(1 , 1 '-biphenyl)-4- yl)methyl)-2-(n-propyl)-4-ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H-imidazole Note that throughout the text when an alkyl substituent is mentioned, the normal alkyl structure is meant (e.g. butyl is n-butyl) unless otherwise specified. However, in the definition of radicals above (e.g. R 3 ), both branched and straight chains are included in the scope of alkyl, alkenyl and alkynyl. The term aryl is meant to include phenyl, biphenyl, napthyl, or fluorenyl group optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, Cι-C4-alkyl, Cι-C4-alkoxy, -CF3, halo, -NO2, -CO2H, -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι -C4-3lkyl), -N(Cι -C4-3lkyl)2. The term heteroaryl is meant to include unsubstituted, monosubstituted or disubstituted 5- to 10-membered mono- or bicyclic aromatic rings which can optionally contain from 1 to 3 heteroatoms selected from the group consisting of O, N, and S. Included in the definition of the group heteroaryl, but not limited to, are the following: pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1 ,3,5-triazinyl, furyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, benzofuranyl, benzothiophenyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, indolin-2-onyl, indolinyl, indolyl, pyrrolyl, quinonlinyl and isoquinolinyl. Particularly preferred are 2-, 3-, or 4-pyridyl; 2-, or 3-furyl; 2-, or 3-thiophenyl; 2-, 3-, or 4-quinolinyl; or 1-, 3-, or 4-isoquinolinyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, Cι -C4-alkyl, Cι -C4-alkoxy, -CF3, halo, -N02, -CO2H, -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι-C4-al yl), -N(Cι -C4-3lkyl)2. The term arylene is meant to include a phenyl, biphenyl, napthyl, or fluorenyl group which is used as a link for two groups to form a chain. Included in the definition of arylene, but not limited to, are the following isomeric linkers: 1 ,2-phenyl, 1 ,3-phenyl, 1 ,4-phenyl; 4,4'-biphenyl, 4,3'-biphenyl, 4,2'-biphenyl, 2.4'-biphenyl, 2,3'-biphenyl, 2,2'-biphenyl, 3,4'- biphenyl, 3,3'-biphenyl, 3,2'-biphenyl,; 1 ,2-napthyl, 1 ,3-napthyl, 1 ,4-napthyl, 1 ,5-napthyl, 1 ,6-napthyl, 1 ,7-napthyl, 1 ,8-napthyl, 2,6-napthyl, 2,3-napthyl; 1 ,4-fluorenyl. Particularly preferred are 1 ,2-phenyl, 1 ,3-phenyl, 1 ,4-phenyl, 4,4'-biphenyl, 3,3'-biphenyl, and 2,2'-biphenyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, C1-C4- alkyl, Cι-C4-alkoxy, -CF3, halo, -NO2, -CO2H, -C02CH3, -Cθ2-benzyl, -NH2, -NH(Cι -C4-alkyl), -N(Cι -C4-alkyl)2. The term heteroarylene is meant to include unsubstituted 5- to 10- membered aromatic ring which can optionally contain from 1 to 3 heteroatoms selected from the group consisting of 0, N, and S which is used as a link for two groups to form a chain. Included in the definition of the group heteroaryl, but not limited to, are the following: 2,3-pyridyl, 2,4-pyridyl, 2,5-pyridyl, 2,6- pyridyl, 3,4-pyridyl, 3,5-pyridyl, 3,6-pyridyl; 2,3-furyl, 2,4-furyl, 2,5-furyl; 2,3- thiophenyl, 2,4-thiophenyl, 2,5-thiophenyl; 4,5-imidazolyl, 4,5-oxazolyl; 4,5- thiazolyl; 2,3-benzofuranyl; 2,3-benzothiophenyl; 2,3-benzimidazolyl; 2,3- benzoxazolyl; 2,3-benzothiazolyl; 3,4-indolin-2-onyl; 2,4-indolinyl; 2,4-indolyl; 2,4-pyrrolyl; 2, 4-quinolinyl, 2,5-quinolinyl, 4,6-quinolinyl; 3, 4-isoquinolinyl, 1 ,5- isoquinolinyl. Particularly preferred are 2,3-pyridyl, 3,4-pyridyl, 2,3-furyl, 3,4- furyl 2,3-thiophenyl, 3,4-thiophenyl, 2,3-quinolinyl, 3,4-quinolinyl and 1 ,4- isoquinolinyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, Ci -C4-alkyl, Ci -C4-3lkoxy, -CF3, halo, -NO2, -CO2H, -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι -C4-alkyl), -N(Cι - C4-slkyl)2. Pharmaceutically acceptable salts include both the metallic (inorganic) salts and organic salts; a non-exhaustive list of which is given in Remington's Pharmaceutical Sciences 17th Edition, pg. 1418 (1985). It is well known to one skilled in the art that an appropriate salt form is chosen based on physical and chemical stability, flowability, hydroscopicity and solubility. Preferred salts of this invention for the reasons cited above include potassium, sodium, calcium and ammonium salts. Also within the scope of this invention are pharmaceutical compositions comprising a suitable pharmaceutical carrier and a novel compound of Formula (I), (II) or (III), and methods of using the novel compounds of Formula (I), (II) or (III), to treat hypertension and congestive heart failure. The pharmaceutical compositions can optionally contain one or more other therapeutic agents, such as a diuretic, an angiotensin I converting enzyme (ACE) inhibitor or a non-steroidal antiinflammatory drug (NSAID). Also within the scope of this invention is a method of preventing renal failure resulting from administration of a NSAID which comprises administering a novel compound of Formula (I) in stepwise or physical combination with the NSAID. The compounds of this invention can also be used as diagnostic agents to test the renin angiotensin system. It should be noted in the foregoing structural formula, when a radical can be a substituent in more than one previously defined radical, that first radical (R # , B or y) can be selected independently in each previously defined radical. For example, Rl and R 2 can each be -CONHOR "1 2 . R 12 need not be the same substituent in each of R 1 and R 2 , but can be selected independently for each of them. Or if, for example, the same R group (let us take R , for instance) appears twice in a molecule, each of those R groups is independent of each other (one R 2 group may be -CONHOR 1 2 , while the other R 2 group may be -CN). It is understood that many of the compounds of the present invention contain one or more chiral centers and that these stereoisomers may possess distinct physical and biological properties. The present invention comprises all of the stereoisomers or mixtures thereof. If the pure enantiomers or diastereomers are desired, they may be prepared using starting materials with the appropriate stereochemistry, or may be separated from mixtures of undesired stereoisomers by standard techniques, including chiral chromatography and recrystallization of diastereomeric salts. Detailed Description of the Invention Synthesis The novel compounds of Formula (I), (II) or (III) may be prepared using the reactions and techniques described in this section. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformation being effected. It is understood by those skilled in the art of organic synthesis that the functionality present on the imidazole and other portions of the molecule must be consistent with the chemical transformations proposed. This will frequently necessitate judgement as to the order of synthetic steps, protecting groups required, and deprotection conditions. Throughout the following section, not all compounds of Formula (I), (II) or (III) falling into a given class may necessarily be prepared by all methods described for that class. Substituents on the starting materials may be incompatible with some of the reaction conditions required in some of the methods described. Such restrictions to the substituents which are compatible with the reaction conditions will be readily apparent to one skilled in the art and alternative methods described must then be used. The imidazole precursors in this application may be prepared as described in U.S. patents 5,137,902 and 5,138,069, in PCT U.S. Application 90/03683 and in European Application EP465.368 (see also Australian Patent AU-A-80163/91 ) and in U. S. Application (07/544557), which are hereby incorporated by reference. When L1 is -C0 2 - and A is -(CH2)n-L 1 -B-(T) y -(B) y -X 2 -(B)y-R28 (subheading (a) of A in the scope of this application) then A may be synthesized by simply alkylating the corresponding free carboxylic acid A = -(CH2)n-COOH of structure (2) with X-B-(T) y -(B) y -X 2 -(B) y -R28 , where X is the corresponding chloride, bromide, tosylate or mesylate in an inert solvent in the presence of an acid scavenger such as potassium carbonate or triethylamine at room temperature to the reflux temperature of the solvent. Common inert solvents include THF, DMF, DMSO, etc. If B is longer than a methylene (CH2), then to facilitate alkylation, it might be necessary to add some sodium iodide . An example of this alkylation is shown below when for A, subheading (a) and going from left to right, B = CH2, T = Ph, y = 1 , y = 0, Or in general, the synthesis may be summarized as in Scheme 1 : Scheme 1 The entire side chain need not be fully elaborated in order to perform this alkylation. For example, instead of alkylating with X-B-(T) y -(B)y-X 2 -(B) y - R28 , one may alkylate with X-B-(T) y -(B) y -X 2 '. X 2' in this case must be a group which can be easily transformed into X 2 -(B) y -R 2 8 via condensation reactions. Therefore this synthetic route applies only where X is a group such as one of the following: amides (-CONR 1 *-, -NR 1 1a CO-), ureas (- NRHaCONR 1 H sulfonamides (-S0 2 NR16-, -NR16S0 2 -), acysulfonamides (-S0 2 NRHaCO-, -CONRHaso 2 -), sulfonylcarbamates (-OCONR 1 iaso -), sulfonylureas (-S0 2 NRiiacONRiib. i -NRHacθNRi 1 bso 2 -), sulfonylsulfonamides (-Sθ2NR 11a Sθ2-), and aminoacylsulfonamides (- C0NR 11 aS0 2 NR 11 b-, -NR 1 iaS0 2 NR 11 bCO-). All of the above groups or linkages may be formed via condensation reactions, which are exemplified in european patent application EPA 400 835, published December 5, 1990. For example, if one were to synthesize X 2 = -CONR 113 -, then one may alkylate the imidazole-5-carboxyl group with X-B-(T)y-(B) -COO-CH2Ph. Subsequent hydrogenation over palladium on carbon in an alcohol solvent yields the free carboxylic acid A = -(CH2)n-COO-B-(T) y -(B)y-COOH. Coupling with amine NHR 11a -(B) y -R28 using, for example, N.N'-diclohexylcarbodiimide in DMF or THF as solvent yields A = -(CH 2 )n-COO-B-(T) y -(B) y -CONR i 1 a-(B) y -R28. Similar types of synthetic schemes can be applied to the other X group containing side-chains mentioned in this paragraph. Amides wherein L 1 = -CONR 11a - may be synthesized by the procedures shown in Scheme 2. Amine (5) is coupled to carboxylic acid (2) using a diimide coupling reagent such as N,N'-dicyclohexylcarbodiimide, etc., in an inert solvent such as DMF to yield amide (6). Another procedure involves converting carboxylic acid (2) into an acid chloride with for example thionyl chloride or oxallyl chloride, procedures familiar to one skilled in the art. This acid chloride is then coupled with amine (5) by simply mixing the two together in an inert solvent, such Scheme 2 1a -(CH 2 -(T) y -(CH 2 ) y -X ? 8 as methylene chloride over an acid scavenger such as potassium carbonate at 0°C to room temperature to yield amide (6). Alternatively, The entire side chain need not be fully elaborated in order to perform this coupling. For example, instead of coupling with HR 11a N-B-(T) y -(B) y -X 2 -(B) y -R28 , one may couple with HR 11a N-B-(T) y -(B) y -X 2' . Thus coupling of carboxylic acid (2) with amine (7) under the above described coupling conditions yields amide (8) which can be subsequently elaborated into amide (6). This of course can only be done if the X 2 linker is one which can be formed by condensation reactions, as was described in the section under L 1 = -COO-. Carbamates wherein L 1 = -NR 11a C0 2 - may be synthesized by the procedures shown in Scheme 3. Here amine (9) is reacted with chloroformate (10) either in the presence of aqueous base (Schotten- Baumann reaction: E. Baumann, Ber. Deut. Chem. Ges. 1886,19, 3218.) or in the presence of an acid scavenger (either 1 equivalent or excess) such as pyridine, triethylamine, or Scheme 3. CI-CO-0-(CKt) n -(T) y -(CH y -X 2 -(CH 2 )y-R 28 + CI-CO-0-(C4) n -(T) y -(CHd y -X 2' ir~-(CH-) n - a CO z (C 2 ) n --(T) y -(C ^ -X z 12 13 potassium carbonate to yield carbamate (11). If the reaction is sluggish, the chlorofomate might have to be activated with 4-N,N-dimethylaminopyridine, either catalytic or excess. The reaction is done in an inert solvent such as methylene chloride or THF, etc. at O °C or room temperature or higher. Likewise as seen earlier, the side-chain may be constructed in two steps, namely reaction of amine (9) with chloroformate (12) to yield carbamate (13) followed by elaboration to carbamate (11 ). This of course can only be done if the X 2 linker is one which can be formed by condensation reactions, as was described in the section under L 1 = -COO-. Another synthesis of carbamates L 1 = -NR 11a C0 2 - involves first reacting amine (9) (R 11a = H) (synthesis described in U.S. Patent 5,138,069) with carbonyldiimidazole in an inert solvent such as THF or DMF at room temperature or with some heating to yield an isocyanate (14) as shown in Scheme 4. Further reaction with an alcohol (15) in an inert solvent with or without heat yields carbamate (11 ). Of course, as in Scheme 3, the synthesis of the side-chain can also be performed stepwise if X 2 can be formed via condensation reactions as was discussed earlier. Scheme 4 16 When n = 0 in Schemes 3 and 4, then there is a carbamate group connected directly to the imidazole 5-position of (9) or (9a). The corresponding isocyanate starting material may be made by Curtius rearrangement (T.L. Capson, CD. Poulter Tet. Lett. 1982, 25, 3515) of the corresponding acyl azide as shown in Scheme 5. Thus, carboxylic acid (17) (prepared as in U.S. PATENT 4,760,083) can be converted to its acid chloride by procedures familiar to one skilled in the art. Subsequent reaction with sodium azide yields acyl azide (19) which is heated to undergo Curtius rearrangement with nitrogen expulsion to yield isocyanate (14a). Heating acyl azide (19) in the presence of alcohol (15) will yield carbamate (11 ) directly (T.L Capson, ibid.). If the alcohol is 2-trimethylsilylethanol, then the resulting carbamate (20) may be decomposed with fluoride ion (T.L. Capson, ibid.) to the amine (21) which can be used to make other carbamate side-chains (or ureas and amides, as seen subsequently). Amine (21 ) may undergo reductive amination by procedures familiar to one skilled in the art to yield alkylated amine (21a). The Curtius rearrangement may be performed in "one pot" by heating carboxylic acid (17) with diphenylphosphorylazide to yield isocyanate (14a) which again can be reacted in the same pot with an alcohol to yield a carbamate (T. Shiori, K. Ninomiya, S. Yamada J. Am. Chem. Soc. 1972, 94, 6203. Yet another synthesis of amine (21 ) is shown below. Here an unsubstituted imidazole at the 5-position is nitrated with HNO3 and H2SO4 under standard conditions. Then the nitro group is reduced with hydrogen over palladium on carbon in an alcohol solvent also under standard conditions to yield (21). reduction 21 Scheme 5 21a 21 20 Taking amines (9), (9a), (21 ), or (21a) and reacting with carbamoyl chloride (22) (formed from phosgene and an amine: H. Hopff, H. Ohlinger Angew. Chem. 1949, 61, 183) will yield urea (23) (Scheme 6). Likewise, primary amines (9) and (21 ) may be converted to the corresponding isocyanate as seen earlier and then reacted with an amine to yield urea (23). For example, reaction of isocyanate (14) with an amine such as (5) will yield urea (23). Conversely, amines (9), (9a), (21), or (21a) can be reacted with isocyanate (24) to yield urea (23). Of course, as in Scheme 3, the synthesis of the side-chains discussed in this paragraph can also be performed stepwise if X 2 can be formed via condensation reactions as was discussed earlier. Scheme 6 The synthesis of -(CH2) n -L 1 -B-(T) y -(B) y -X 2 -(B) y -R 8 where X is either a ketone, ether or thioether are summarized in Scheme 7. Aldehyde (25) may be reacted with Grignard reagent (26) in an inert solvent such as ether or THF at 0 °C to room temperature or with some heating to yield alcohol (27). Oxidation by a variety of methods familiar to one skilled in the art yields ketone (28). These methods include the use of PCC (pyridinium chlorochromate: E.J. Corey, J.W. Suggs Tet. Lett., 1975, 2647), pyridinium dichromate in methylene chloride (E.J. Corey, G. Schmidt Tet. Lett., 1979, 399), the Swern oxidation using DMSO and trifluoroacetic anhydride (K. Omura, A. K. Sharma, D. Swern, J. Org. Chem., 1976, 41, 957), the Dess- Martin Periodinane oxidation (D.B. Dess, J.C. Martin, J. Org. Chem. 1983, 48, 4156 and J.P. Burkhart, N.P. Peet, P. Bey, Tet. Lett. 1988, 29, 3433) or a Bobbin oxidation using 4-acetylamino-2,2,6,6-tetramethylpiperidinyl-1-oxyl and toluenesulfonic acid (Z. Ma, J.M. Bobbitt, J. Org. Chem., 1991 , 56, 6110). Metal alkoxide (29) is reacted with bromide (30) to undergo SN2 displacement in an inert solvent such as DMF, DMSO, or THF, with or without the presence of an iodide salt, to yield ether (31 ). Likewise, the bromide and alkoxide moieties may be interchanged so that bromide (32) is reacted with alkoxide (33) to yield ether (31 ) under the same conditions. The oxygen atom may be replaced with sulfur to yield thioether products. Once the side-chain is synthesized, the THP group is removed using aqueous acid and the alcohol can be converted to the bromide via standard methods (PBr3, CBr4 & Ph3P, etc.) or made into a leaving group such as a tosylate, mesylate or triflate by procedures familiar to one skilled in the art. These can be reacted further with sodium azide in DMSO to form the azide (J.M. Muchowski, Can. J. Chem. 1971 , 49, 2023) which can be hydrogenated to the amine using hydrogen over palladium on carbon. Or the bromide, tosylate, mesylate or triflate may be reacted with ammonia to yield the amine directly. Scheme 7 X 1 m -CO- X* = -O- (or -S-) X-(CH 2 )_,.rr) y -(CH 2 ) y -CHO X-<CHj) n .(TV(CH 2 V,-CH 2 θ- * X-tCH^fO^CH j ^-CH^r (X - OTHP) 25 (X - OTHP) 29 (X - OTHP) 32 BrMgCH 2 -<CH 2 ) y .--(R 2β ) BfCH 2 -(CH 2 ) y .,-R 21 -OCH j -ICH^.-fR 28 ) 26 30 33 X-(CH 2 ) n .-(T) y -(CH 2 ) y -CH(OH)-CH 2 -(CH 2 ) y .,R a X-(CH 2 ) n .-(T) y -(CH 2 ),.,-CH r θ-CH 2 -(CH 2 ) y .,-R ω 27 31 [O] X-(CH 2 ) n .-(T) y -(CH 2 ) y -θ-(CH 2 ) y -R 2β X-(CH 2 ) n ,(T) y -(CH 2 ) y -CO-CH 2 -<CH 2 ) y .,-R 2e III » X-(CH 2 ) n .-(T) y -(CH 2 ) y -CO-(CH 2 ) y -R 2β If any y is zero in (CH2) y of (31 ) , then they are aryl-ethers or- thioethers. These are synthesized employing variations of the Ullmann aryl ether synthesis (A.A. Moroz, M.S. Shvartssberg Russ. Chem. Rev., 1974, 43, 679). Side-chains represented in the scope by A subheading (b) (-(CH2)rr j_1 -B-T-(B) y -R28 ) may be synthesized by the methods described in A subheading (a). When y equals zero, then we have a biaryl, a heteroaryl-aryl, an aryl-heteroaryl, and biheteroaryl system. These compounds may be synthesized by employing aromatic cross-coupling reactions familiar to one skilled in the art. For example, there is the Stille Coupling (A.M. Echavarren, J.K. Stille, J. Am. Chem. Soc. 1987, 109, 5478; T.R. Bailey, Tet. Lett. 1986, 4407); Suzuki Coupling (N. Miyaura, T. Yanagi, A. Suzuki Syn. Comm. 1981 , 11, 513; J.-m. Fu, V. Snieckus Tet. Lett. 1990, 31, 1665); Negishi Coupling (E. Negishi, A.O. King, N. Okukado J. Org. Chem. 1977, 42, 1821 ; A.S. Bell, D.A. Roberts, K.S. Ruddock, 7e/. Lett. 1988, 29, 5013); Ullmann Coupling (W.J. Thompson, J. Gaudino J. Org. Chem. 1984, 49, 5237); and other reactions and references summarized in a review (V.N. Kalinin Synthesis 1992, 413). When y equals one, one can make the biaryl, heteroaryl-aryl, aryl-heteroaryl, and biheteroaryl methylene compounds (B = CH2) via the Negishi coupling (ibid.). One can also make them from the corresponding ketones (C=0) by simply reducing the ketone to the methylene via hydrogenation over palladium on carbon. For y>1 , one may employ the Wittig reaction (familiar to one skilled in the art) to make the corresponding biaryl substituted alkenes which can be reduced (hydrogenated over Pd on carbon) to the corresponding alkyl. Side-chains represented in the scope by A subheading (c) may be synthesized by the methods described in A subheading (a). Side-chains represented in the scope by A subheading (d) may be synthesized by the methods described in A subheading (a) with the appropriate substitution on T to permit elaboration to R 29 (Scheme 8). For example, if T is substituted with a protected alcohol such as CH 2 (CH 2 ) n OTHP, where n = 0-6, then the alcohol can be deprotected with aqueous acid or HCI in MeOH to yield the free alcohol. Subsequent oxidation, as with Mnθ 2 (if n = 0), PCC (pyridinium chlorochromate: E.J. Corey, J.W. Suggs Tet. Lett., 1975, 2647), pyridinium dichromate in methylene chloride (E.J. Corey, G. Schmidt Tet. Lett., 1979, 399), Swern oxidation using DMSO and trifluoroacetic anhydride (K. Omura, A. K. Sharma, D. Swern, J. Org. Chem., 1976, 41, 957), Dess-Martin Periodinate oxidation (D.B. Dess, J.C. Martin, J. Org. Chem. 1983, 48, 4156 and J.P. Burkhart, N.P. Peet, P. Bey, Tet. Lett. 1988, 29, 3433) or a Bobbitt oxidation using 4-acetylamino-2,2,6,6-tetramethylpiperidinyl-1-oxyl and toluenesulfonic acid (Z. Ma, J.M. Bobbitt, J. Org. Chem., 1991 , 56, 6110) affords aldehyde (35). An amine can be protected, for example with 3,4- dimethoxybenzyl groups. Thus a carboxylic acid can be converted into its corresponding bis(3,4-dimethoxybenzyl)amine amide by coupling methods familiar to one skilled in the art. Subsequent hydrogenation or acid cleavage yields amide (36) (M.I. Jones, C. Froussios, D.A. Evans J. Chem. Soc. Chem. Comm. ,1976, 472, ). A nitro group is a latent amino functionality. Thus R29 ' = NO2 can be reduced by a variety of methods familiar to one skilled in the art, the easiest of which is simple hydrogenation over a noble metal catalyst to yield an amine. Subsequent refluxing with ethyl formate in an inert solvent yields formamide (37). R29 ' = S-C v F2v + ι may be oxidized by one equivalent of hydrogen peroxide to yield sulfoxide (38) (r = 1 ) or with excess peroxide to yield sulfone (38) (r =2) (R.L Shriner, H.C. Struck, W.J. Jorison J. Am. Chem. Soc, 1930, 52, 2066; O. Hinsberg Chem. Ber. 1910, 43, 289). R29 ' = S- C v F2 +ι may be synthesized via SN2 displacement chemistry by a sulfur nucleophile with an activated leaving group on the perfluoroalkyl group (L.M. Yagupolskii, et al. Synthesis 1978, 835). A variation of the preceding is an electochemical SN2 displacement to yield S-perfluoroalkyl compounds (J. Pinson, J.-M. Saveant J. Am. Chem. Soc. 1991 , 113, 6872). Another synthesis would be via reduction of the corresponding perfluoroalkylsulfone, with, for example, diisobutylaluminum hydride (Gardner, et al. Can. J. Chem. 1973, 51, 1419). Alkylsulfones are readily available from SN2 displacement chemistry by sulfinic acid salts (Meek and Fowler J. Org. Chem. 1968, 33, 3422), in this case perfluoroalkylsulfinic acid salts. If the sulfide is directly attached to T, then a Friedel-Crafts reaction can be used to directly attach the perfluoroalkylsulfur group to T using C F2 V +1-S-CI in the presence of SnCU (A. Hass, V. Hellwig Chem. Ber. 1976, 109, 2475). This product in turn can be oxidized to the corresponding sulfoxides and sulfones, selectively. Perfluoroamide (39) may be made from the corresponding deprotected carboxylic acid as shown by diimide coupling methods familiar to one skilled in the art. R 29 = -CO-C F2v + ι and -0-C v F2 + ι must be assembled before L 1 , the linkage to the imidazole, is formed. For the other R29 groups, one has the option of preassembling the side-chain before L 1 is formed or after it is formed. The R 2 9 = -CO-C v F2 V+ ι and -0-C v F2 V+ ι groups can be prepared easily from commercially available starting materials, the procedures of which are familiar to one skilled in the art. For example, a perfluoroalkanoyl-arene or -heteroarene may undergo Friedel-Crafts alkylation with CI(CH2)nCI to yield CI-(CH2)n-T-(B) y -CO-C v F2v + i. This in turn may be elaborated by any of a number of methods previously shown to yield imidazole (34) where R 2 9 ' = R29 = -CO-C v F2v+ι. The same is true for elaborating perfluoroalkyloxy-arene or -heteroarene to R29 ' = R29 = -0-C v F2 V +ι. Grignard reagents will react with anhydrides of perfluoroalkanoic acids to yield perfluoroalkylketones (United Kingdom Patent, number 2,210,881 , issued to Imperial Chemical Industries). Friedel-Crafts acylation of perfluoalkanoyl species directly onto T will also yield perfluoroalkanoyl ketones attached directly to T (T.R. Forbus, Jr. J. Org, Chem. 1979, 44, 313; J.W. Harbuck, H. Rapaport J. Org. Chem,, 1972, 37, 3618). Perfluoroalkoxyhalides will add across alkenes to yield perfluoroalkyl haloalkyl ethers (O. Lerman, et al. J. Org. Chem. 1980, 45, 4122; D.H.R. Barton, et al. J. Chem. Soc. P. I, 1977, 2604; L.R. Anderson J. Org. Chem. 1970, 35, 3730). Subsequent removal of the chlorine with tribuyltin hydride with a radical initiator will yield the perfluoroalkyl ether, familiar to one skilled in the art. If fluorine (or chlorine, for that matter) was used in the perfluoroalkoxyhalide, then subsequent dehydrofluorination with base followed by hydrogenation over a noble metal catalyst will yield the perfluoroalkyl alkyl ether, by procedures familiar to one skilled in the art. The perfluoroalkoxy group may be directly attached to T via the Ullmann ether synthesis (Moroz and Schvartsberg Russ. Chem. Rev. 1974, 43, 679). Scheme 8 im-(CH2)_,-l B-T-(B) y -CONH2 36 39 i -fCH^-L'-B-T-CBl.-SfO C^,, 38 When A is -(CH2)n-L 1 -(T)-(B) y -X 2 -(B) y -R28 (subheading (e) of A in the scope of this application) then A may be synthesized by simply taking carboxylic acid (2) and coupling it with HO-(T)-(B) y -X 2 -(B) y -R 2 8 to yield L 1 = -CO2-. This coupling is carried out via diimide coupling methods familiar to one skilled in the art (N,N-dicyclohexylcarbodiimide). Another way is via conversion of the carboxylic acid group of (2) to an acid chloride which can be reacted with the metal alkoxide of HO-(T)-(B) y -X 2 -(B) y -R 2 8 formed from reaction with NaH or KH in DMF or another inert solvent, or with the free alcohol HO-(T)-(B) y -X 2 -(B)y-R28 using Schotten-Baumann conditions discussed previously. Likewise, the same procedures can be used with HNRHa-(T)-(B)y-X -(B) y -R28 to yield L1 = -CONR *-. Procedures in Schemes 3-6 can be used to synthesize A = -(CH2)n-NR 1 a Cθ2-(T)-(B) y - X -(B) y -R28 and -(CH2)n-NR 11 a CONRiib (T)-(B) y -X 2 -(B) y -R28 . Of course, as in Scheme 3, the synthesis of the side-chain can also be performed stepwise if X 2 can be formed via condensation reactions as was discussed earlier. If X 2 cannot be formed by condensation reactions as when it is a ketone, ether, or thioether, then the syntheses of these side-chains follows basically the pathway described in Scheme 7. This is true for all of the X 2 containing side-chains described in the scope and listed under A. Removal of X 2 from A subheading (e), the side-chain which was previously discussed above, leads to the side-chain described under A subheading (f), or namely -(CH2)n-L 1 -(T)-(B) y -R 28 . This side-chain may be synthesized by the procedures described for A when A is -(CH2)n-L 1 -(T)- (B) y -X 2 -(B) y -R 28 (subheading (e)). When y = 0, then any of the aryl cross- coupling reactions described previously may be used to synthesize the carbon-carbon bond between T and R 28 . When y = 1 , then the Negishi coupling reaction may be used to synthesize the T-CH2-R 28 unit. One can also make them from the corresponding ketones by simply reducing the ketone to the methylene via hydrogenation over palladium on carbon. For y>1 , one may employ the Wittig reaction (familiar to one skilled in the art) to make the corresponding biaryl , or biheteroaryl or aryl-heteroaryl substituted alkenes which can be reduced to the corresponding alkyl to yield the T- (CH 2 ) n -R 28 unit. Removal of R 28 from the side-chain described in A, subheading (e), leads to the side-chain described under A subheading (g), or namely -(CH2)rr L 1 -(T)-(B) y -X 2 -B . Here the synthesis is basically the same as described in A subheading (e). A is -(CH2)n-L 1 -(CRi9R20). D .(T) y -(B) y -χ3-(B) y -R28 (subheading (h)) can be synthesized by the methods described in Schemes 9 and 10. Scheme 9 41 reaction, then synthesis similar to that in Scheme 7 Br (CH 2 ) n - (T) r (Chi 2 )y-X 3 -(CH 2 )y-R 28 42 (CH 2 ) n - (T)y-(CH2)y-X 3 -(Cϋ>)y-R 28 43 44 Wittig Reaction, or Horner-Emmons Modification of the 1 Wittig Reaction 45 Scheme 9 describes the synthesis of D = alkenyl where the double bond is directly connected to CR 19 R 2n . A similar reaction sequence employing a Wittig reaction can be used to synthesize alkenes where the double bond is not connected directly to the CR 19 R 2 0 methylene group. Only the appropriate aldehyde (analog of (43) must be used to place the double bond where necessary. The synthetic scheme begins with the synthesis of (40). If X 3 cannot be made from condensation reactions as described previously, then X 3' of (40) will be equal to X 3 -(CH2)y-R 28 . One may use the reaction sequences described in Scheme 7 to make these compounds. If X 3 can be made via condensation reactions, then a suitable precursor, X 3' is present instead to make the synthesis easier. However, given the nature of the manipulations, sometimes the entire side-chain may be used where X 3 -(CH 2 )y-R 28 is present instead of X 3' and X 3 is made from condensation readtions. It is up to one familiar in the art to decide when to procede with the entire side-chain, or when to use a precursor containing X 3' . Compound (40) may be synthesized by a number of routes, only some of which are disclosed in Scheme 9. For example, if n'=0 and y=1 of (T) y , then the methanol side-chain may be alkylated onto the aryl group T (or heterocyclic group) by the methods shown using formaldehyde or its equivalents, for example paraformaldehyde (G. Olah "Friedel-Crafts and Related Reactions," Interscience, New York, (1963) volume 2, pp. 597-640; N.S. Narasimhan, R.S. Mali, B.S. Kulkarni Tet. Lett., 1981 , 2797). When n'=1 , then ethylene oxide or its equivalents may be used as shown in Scheme 9 (J. March "Advanced Organic Chemistry," Wiley-lnterscience, 1985, 3rd ed., p. 480; H.A. Patel, D.B. MacLean Can. J. Chem. 1983, 61, 7). When n'=2 or more, then the appropriate alkyl side-chain may be attached via a Wittig reaction (to make an intermediate alkene) followed by reduction to the alkane. If there is no T group (y=0), then one has simple X 3' substituted alcohols, many of which are commercially available. X 3' can be N-phthalimido, -NH- CBZ, carboxylic acid esters, -SO3CH 3 , -Sθ2NH-t-Bu, -S-P where P is a protecting group, etc., all of which can be easily transformed later on into X 3 groups (or compound (41 )), the transformations being familiar to one skilled in the art. The original protected alcohol is deprotected and converted to the bromide (42) as discussed elsewhere and previously. Conversion to the Wittig reagent (44) followed by reaction with aldehyde (43) (wherein X is a group suited for conversion later into L 1 such as a protected alcohol, halogen, a protected nitrogen, etc.) yields alkene (45) (for a summary of the Wittig reaction and the Horner-Emmons modification thereto, see J. March "Advanced Organic Chemistry," Wiley-lnterscience, 1985, 3rd ed., p. 845-854). The sequence can also be reversed in that (43) could in theory be the Wittig reagent and (44) could be the aldehyde piece, both of which can be constructed by the chemistry mentioned in Scheme 9 and elsewhere in this disclosure. The synthetic sequences leading to the incorporation of an alkynyl side-chain are summarized in scheme 10. Scheme 10 (CH 2 )„.- (T) y -(CH j ) y -X T ) y -X 3' 49 55 R 19 R 20 - (CH 2 ) n — ==■ (CH 2 )' n — (T) y -(CH 2 ) .-X'-ICH j ) y -R 2 ■ (CH 2 ) n — (TV(CH 2 ) y -X 9 -(CH 2 ) y -R i » HO HO alkyne within the alkyl chain 50 56 (CH 2 ) y -R 2 60, where y is 1 A terminal alkyne is reacted with either NaNH 2 , Grignard reagents, or BuLi to form the metal acetylide (J. March "Advanced Organic Chemistry," Wiley-lnterscience, 1985, 3rd ed., p. 545), in this case alkynyl lithium (46) using n-BuLi. Reaction of this anion with ketone or aldehyde (47) yields alcohol (49) (see Ziegenbein in Viehe, "Acetylenes" Marcel Dekker, New York, 1969, pp. 207-241 ; Ried, Newer Methods Prep. Org. Chem., 1968, 4, 95). If X 3 can be formed via condensation reactions, then a suitable latent functionality X 3' can be used instead as discussed previously. Subsequent elaboration yields X 3 -containing alcohol (50). This alcohol may be esterified with im-(CH2)n-COOH (2) to yield side-chain A, subheading (h) where D is alkynyl. Likewise, as discussed previously to some extent, alcohol (49) may be esterified with carboxylic acid (2) followed by elaboration to the X 3 - containing side-chain denoted in (50). Esterification procedures are familiar to one skilled in the art. However, one may use a Mitsunobu-type procedure for reacting alcohols (49) and (50) with carboxylic acid (2) under very mild conditions (O. Mitsunobu Synthesis 1981 , 1 ) to yield the side-chain described in A, subheading (h), where D is alkynyl. If the alkyne is not connected directly to CR 19 R 2 , but is found somewhere in the middle of the alkyl chain, then it may be synthesized by the route depicted in going from compounds (51) to (56). The metal acetylide (52) (in this case we have arbitrarily chosen sodium as the metal), may be alkylated with bromide (51 ). The opposite may also be done as shown with acetylide (53) reacting with bromide (54) to form acetylene (55). Intermediate (55) can then be deprotected and coupled to carboxylic acid (2). Or first, the X 3' of (55) is elaborated to X 3 , and then the alcohol deprotected to yield (56) which can be coupled to carboxylic acid (2) in a manner similar to that used for (50). In all of these syntheses, if X 3 cannot be formed by condensation reations (X 3 = CO, S,0, etc.) then the fully elaborated and protected (if necessary) side-chain must be used. Finally, if the acetylene portion is connected directly to T (y is 1 ), then the synthesis follows that of going from compound (57) to (60). Thus, acetylene (57) is coupled in the presence of a palladium catalyst to aryl or heteroaryl iodide or bromide (58) or (59) to yield the aryl or heteroaryl acetylene coupled product (W. Tao, S. Nesbitt, R.F. Heck J. Org. Chem. 1990, 55, 63; A. Walser, et al., J. Med. Chem. 1991 , 34, 1440; T. Sakamoto, M. An-naka, Y. Kondo, H. Yamanaka Chem. Pharm. Bull. 1986, 34, 2754; N.A. Bumagin, V.V. Bykov, I. P. Beletskaya Izv. Akad. Nauk. SSSR. Ser. Khim. 1990, 2665; M.A. De la Rosa, E. Vlarde, A. Guzman Syn. Comm. 1990, 20, 2059; Y. Kondo, H. Yamanaka Chem. Pharm. Bull., 1989, 37, 2933. Deprotection of the alcohol yields (60) which can be esterified as previously discussed. Compounds where L 1 is amide, carbamate and urea may be made as discussed in Schemes 2-6 using the intermediates in Schemes 9 and 10. Side-chains described in A, subheadings (i) through (o) may be made by the procedures described in Schemes 9 and 10 together with those mentioned in the previous discussion in this application. Side-chains described in A, subheading (p), namely -(CH2)n-L 2 -B- (T) y -(B) y -X 2 -(B) y -R28 , where L 2 is a ketone carbonyl (L = CO) may be synthesized by the methods shown in Scheme 11. Scheme 11 63 M im-(CH 2 ) n -CO-(C^) n .-(T) y -(B) y -X 2 -(B) y -R B 65 Scheme 11 , continued im-tCHjønCHO *_. im-fCH^CHfOHJC^ _»- i -fCH^-fCOJ-CHa 62 66 67 im 68 Alcohol (61) (described in U.S. PATENT 5,138,069) is oxidized by methods familiar to one skilled in the art to aldehyde (62). Some of these methods include Mnθ 2 if n+1=1 ; PCC (pyridinium chlorochromate: E.J. Corey, J.W. Suggs Tet. Lett., 1975, 2647); pyridinium dichromate in methylene chloride: E.J. Corey, G. Schmidt Tet. Lett., 1979, 399; Swern oxidation using DMSO and trifluoroacetic anhydride: K. Omura, A. K. Sharma, D. Swern, J. Org. Chem., 1976, 41, 957; Dess-Martin Periodinane oxidation: D.B. Dess, J.C. Martin, J. Org. Chem. 1983, 48, 4156 and J.P. Burkhart, N.P. Peet, P. Bey, Tet. Lett. 1988, 29, 3433; and Bobbitt oxidation using 4-acetylamino-2,2,6,6-tetramethylpiperidinyl-1-oxyl and toluenesulfonic acid: Z. Ma, J.M. Bobbitt, J. Org. Chem., 1991 , 56, 6110. Subsequent reaction of aldehyde (62) with a Grignard reagent or a lithium reagent (obtained via halogen-metal exchange, for example) yields alcohol (63). Here, as discussed previously, X 2' is a suitable precursor to the fully elaborated side-chain containing X 2 , if χ2 ' can be formed via condensation reaction chemistry. If X 2' cannot be formed via condensation chemistry, then the whole side chain, namely MCH 2 (CH2)n'-ι- (T) y -(B)y-X 2 -(B) y -R 28 , is used where X 2 is protected if necessary, with subsequent oxidation yielding ketone (65). Oxidation of alcohol (63) yields ketone (64) which may be elaborated as discussed previously to (65). Oxidation methods to the ketones include those mentioned in the synthesis of aldehyde (62). Another method for making ketone (65) involves alkylating ketone (67) (formed in an analogous manner to ketone (64) but employing methyl Grignard or methyl lithium instead of MCh CH n'-i-O fBJy-X 2' ). Thus ketone (67) is reacted with lithium diisopropylamide (LDA) in THF at -78°C to form enolate (68) where M = Li. This enolate is then alkylated in the same reaction flask with XCH 2 (CH2)n'- 2 -(T) y -(B) y -χ 2' to yield ketone (64). Side-chains described in A, subheading (p), namely -(CH2)n-L 2 -B- (T) y -(B) y -χ2-(B) y -R28 , where L 2 is an amide (L 2 = -NR aCO-) , may be synthesized as depicted in Scheme 12. Amine (9) may be reacted with acid chloride (69) under Schotten-Baumann conditions as discussed previously to Scheme 12 yield amide (70). Alternatively, diimide coupling of carboxylic acid (71 ) with amine (9) also yields amide (70), a procedure familiar to one skilled in the art, for example, the art of peptide synthesis. If X 2 can be made via condensation reactions, then the partial assembly of the side-chain may be carried out going through intermediates(72), (73) or (74) by the same procedures. Scheme 13 shows the syntheses of amine (9) when n = 0. Carboxylic acid (75) (prepared as in U.S. PATENT 5,138,069) is decarboxylated in refluxing decane or another high boiling solvent to yield imidazole (76). Nitration under standard conditions yields nitroimidazole (77). Hydrogenation over palladium on carbon yields aminoimidazole (9a). Reductive amination to put on an R 11a group yields imidazole (9b) (for a review on reductive amination reactions, see Klyuev and Khidekel, Russ. Chem. Rev., 1980, 49, 14). Scheme 13 HN rH 2 S0 4 21 21a (or 9, when n = 0 (or 9, when n = 0) and R 1 a = H) t 70 70 Side-chains described in A, subheadings (q) through (v) may be synthesized by the procedures described previously in this disclosure. Side-chains described in A, subheading (w) wherein the alkene is connected directly to L 2 (as opposed to having a alkyl spacer between the alkene and L 2 ) may be synthesized by the methods shown in Scheme 14. Other alkenes wherein the olefinic portion is located within the alkyl chain may be synthesized by the methods already discussed in this disclosure. Scheme 14 HO^* (CHa),,-— (T) y1 -(CH 2 ) y -X 3 -(CH 2 V-R 28 Γ M ιm 79 Alcohol (41 ) can be oxidized by a variety of methods discussed previously, such as the Swern oxidation, pyridinium chlorochromate, pyridinium dichromate, etc., to yield aldehyde (78). Reaction of this aldehyde with enolate (68) in an aldol reaction yields a,b-unsaturated ketone (79) (Aldol reaction: Nielsen and Houlihan, Org. React, 1968, 16, 1-438). As discussed previously, if X 3 can be formed via condensation reactions, then the entire side-chain need not be fully elaborated as in aldehyde (78). Here, X 3' can be substituted for X 3 -(CH2) y -R 28 , X 3' being a latent functionality, which after the aldol condensation may be converted into X 3 -(CH2)y-R 28 . Another synthesis of ketone (79) would involve a Wittig reaction between aldehyde (78) and Wittig reagent (80), mimicking the chemistry presented in Scheme 9. 80 Compounds where L 2 is -NR 11a CO- may be synthesized by coupling (diimide coupling or Schotten-Baumann reaction, as discussed previously) amines 9, 9a, 21, 21a with a,b-unsaturated carboxylic acids (81) or (82) (or the corresponding acid chlorides), with subsequent elaboration if necessary. 81 82 Alkynes described in A, subheading (w) wherein the alkyne portion is connected directly to the carbonyl group of L 2 in which L 2 is a ketone, may be synthesized by the methods shown in Scheme 15. Scheme 15 83 R e (CH^CO" • (CH2) n . (T) y -(CH 2 ) y -X J -(CH 2 ) y -R 28 ι or im (CH2) n (T) y -(CH 2 VX 3' 87 Acid chloride (83) (made from the corresponding carboxylic acid by simply stirring with thionyl chloride or oxallyl chloride in an inert solvent, procedures familiar to one skilled in the art and discussed previously) may be coupled with alkyne or alkynylstannane (84) or (85) in the presence of catalytic amounts of Cul-(Ph3P)2PdCl2 and triethylamine (for (84)) or Pd(ll) or Pd(0) complexes (for (85)) to yield alkynyl ketone (86) (Y. Tohda, K. Sonogashira, N. Hagihara Synthesis (1977) 777; M.W. Logue, K. Teng J. Org. Chem. (1982) 47, 2549). Other alkynes not directly connected to the ketone carbonyl can be synthesized by procedures already discussed previously. Alkynes described in A, subheading (w) wherein the alkyne portion is connected directly to the carbonyl group of L 2 in which L 2 is -NR 11a CO-, may be synthesized by the methods shown in Scheme 16. Scheme 16 92 Amine (9) is coupled with alkynoic acids (88) or (89) to yield amide (91 ). Coupling methods include diimide, the Schotten-Baumann reaction with the corresponding acid chlorides, both of which were discussed previously. The alkynoic acids may be synthesized from the corresponding alkynes via metallation (in this case with a Grignard reagent to make alkynemagnesium bromide (90)) and quenching with carbon dioxide in an inert solvent such as THF (H. Mayer Helv. Chim. Ada 1963, 46, 650; J. Wotiz, C.A. Hollingworth J. Am. Chem. Soc. 1956, 78, 1221). Intermediates in these metallations might have to be protected, in order for the reaction to succeed. For example, if X 3 is a ketone, then it must be protected, i.e., ketalized, a procedure familiar to one skilled in the art. Of course, intermediates like (92) and (87) (from Scheme 15) may be transformed to the fully elaborated side-chains as previously discussed. Compounds wherein L 2 is -NR 11a CO-, and the alkyne is located within the alkyl chain and not connected directly to the carbonyl group of L 2 may by synthesized by methods already discussed previously in this application. Side-chains described in A, subheadings (x) through (dd) may be synthesized by the procedures described previously in this disclosure. When A of compounds of Formula (I) contains L 3 (where L 3 is -0-, -SO-, -NH-, or -NR 1 1 a -), imidazoles (61 , 93, 95, 98, 99) can be used as starting materials in the synthesis of those side-chains. Such imidazoles can be prepared by the methods outlined in Scheme 17. Thus, treatment of alcohols (61, 93) with thioacetic acid in the presence of a Lewis acid catalyst (e. g. Znl2) would provide (94), which upon saponification with hydroxide ion (e. g. NaOH or KOH) in aqueous or aqueous alcohol solution, would give thiol (95) (J.Y. Gauthier Tet. Lett. 1986, 15). Imidazoles (61 , 93) can be converted to the chloride derivatives (96) by treatment with SOCI2, for example, either neat or in an inert solvent, such as benzene or dichloromethane, between room temperature and the reflux temperature of the mixture. In turn, (96) could be reacted with azide anion (NaN3, KN3) in a suitable sovent (DMSO, DMF, NMP), to give (97), which when reduced with H2 in the presence of a catalyst, such as Pd/C, in alcohol solution, would generate amines (9, 9a, 99). These primary amines could, in turn, be converted to secondary amines (21 , 21a, 98) through reductive amination (a method well-known to those skilled in the art) with an aldehyde, RCHO, and a reducing agent, such as NaCNBHβ or NaBH(OAc)3 (A.F. Abdel-Magrid; C. A. Maryanoff; K.G. Carson, Tet. Lett. 1990, 31, 5595 ) in alcohol solution. Alternatively, these secondary amines could be generated directly from (96) by treatment with a primary amine, R 1 1 a NH2, in the presence of an acid scavenger (e. g. K2CO3, Na2Cθ3) in a suitable solvent (THF, DMF, CH2CI2, benzene). The best route to (21 , 21a, 98) will be determined by the nature and availability of RCHO and R 1 1 a NH2, and the choice will be obvious to one skilled in the art. Synthesis of imidazole (61) has been described here and elsewhere (U.S. Patent 5,138,069). Imidazoles (93) may be prepared by methods shown in Scheme 18. In the cases where m of (CH2)m-OH is two or three, esterification of carboxylic acids (2, 100; U.S. Patent 5,138,069) with an alcohol (e. g. MeOH, EtOH) in combination with a mineral acid (e. g. hydrochloric or sulfuric) between room temperature and the reflux point of the reaction mixture, followed by reduction with a hydride reducing agent (UAIH4, DIBAL-H, Red-AI®) in a suitable solvent (THF, ether) would yield (93, m = 2, 3). On the other hand, Wittig reaction (a method known to one skilled in the art) of aldehyde (62) with a suitably protected phosphorane of the proper chain length (Agric. Biol. Chem. 1984, 48, 1731 ; Synthesis 1985, 12, 1161 ) would yield an olefin. Hydrogenation over a catalyst such as Pd/C, followed by removal of the protecting group with, for example, dilute mineral acid (HCI, H2SO4) or catalytic organic acid (p-TsOH, CSA) in a solvent such as THF or MeOH, would provide (93, m=3,4,5). Scheme 17 9, 9a, 99 SCHEME 18 For subheadings (ee), (ff), (gg) and (hh), A may be synthesized by alkylating imidazole (61, 93, 95, 98, 99) with X-(CH2)n'-(T)y-(CH2)y-X 2 - (CH2)y-R 28 , as in the specific case of (ee), as shown in Scheme 19. Likewise, for subheadings (ff), (gg) and (hh), alkylation with the requisite alkylating agent would give A. In this alkylation, X would be a halide or sulfonate group, and the reaction would be run in an inert solvent such as THF, DMF, or DMSO between room temperature and the reflux temperature, in the presence of an acid scavenger, (e. g. Et3N or K2CO3) or strong base (e. g. NaH or KH). In some cases, it may prove advantageous to add a source of iodide ion to the reaction (e. g. Nal, Kl, or n-Bu4N+l"). Such cases would be obvious to one skilled in the art. After the alkylation, to convert L 3' = -S- to L 3 = -SO-, an oxidant such as hydrogen peroxide (R.L Shriner; H.C. Struck; W.J. Jorison J. Am. Chem. Soc, 1930, 52, 2066) or sodium periodate (B.M. Trost, R.A. Kuns J. Org. Chem. 1974, 39, 2648), or an organic peracid (H. Richtzenhain; B. Alfredson Chem. Ber. ' 1953, 86, 142) or bromine/aqueous potassium hydrogen carbonate (J. Drabowicz; W. Midura; M. Mikolajczyk Synthesis, 1979, 39) can be used. As described previously in this disclosure, when X 2 in (ee) and (gg) is a condensable function, it may not be necessary to elaborate the entire side chain prior to alkylation. Scheme 19 61 , 93, 95, 98, 99 (CH 2 ) m -L 3 -(CH 2 ) n -(T) y -(CH 2 ) y -X 2 -(CH 2 )y-R 28 101 A general method for the preparation of A groups (ii), (jj), and (kk) is shown in Scheme 20 for the particular case of (ii). Alkylation of H-L 3 '-T-(B)y- X 2 -(B) y -R 2 8 (where H-L 3' represents H-0-; H-S-, or H-NR11a.) w j t chloride (96) in the presence of an acid scavenger or strong base in an inert solvent with or without added iodide ion, followed by oxidation (when L 3 is -SO-), would yield (102). When X 2 in (ii) and (kk) is a condensable function, it may not be necessary to elaborate the entire side chain prior to alkylation. A possible method for preparation of A groups (II) through (ss) is shown in Scheme 21 for the case of (II). This method is analogous in all respects to that described above for subheadings (ee) through (hh). Following alkylation, oxidation (when L 3 is -SO-) would give (103). As above, when χ6 (subheadings (II) and (nn)) is a condensable function or X 7 is present, it may not be necessary to elaborate the entire side chain prior to alkylation. Scheme 20 Scheme 21 X-(CR 1 R 20 )-D-(T) y -(B) v -X 3 -(B) v -R 21 acid scavenger or strong base, I ' (optional), inert solvent 103 Side-chains described in A, subheading (tt) and ( υ) may be made by the methods shown in Schemes 22 and 23. 106 All commercially All commercially available available All commercially All commercially available available Scheme 23 H 110 111 The 2-, 3-, and 4-pyridinecarboxylic acids, the 2-, 3-, and 4- pyridineacetic acids and the 2-, 3-, and 4-pyridinepropanoic acids are readily available from commercial sources or available with slight synthetic manipulation from commercial sources as shown in Scheme 22. For example, pyridinecarboxaldehydes (104) (commercially available) may undergo the Wittig reaction followed by saponification to yield pyridinepropenoic acids (105). Hydrogenation using palladium on carbon in an alcohol catalyst yields pyridinepropanoic acid (107). All of these types of reactions have been discussed previously. The pyridine alkanoic acids can then be hydrogenated with platinum oxide or rhodium on alumina (P.L. Omstein, US patent number 4,968, 678, issued November 6, 1990) to yield the corresponding piperidine derivatives (111) (Scheme 23). Esterification by refluxing in methanol containing HCI (a procedure familiar to one skilled in the art) yields ester (112). Lithium aluminum hydride reduction yields alcohol (113) (P.L. Omstein.ibid). Condensing aminoalcohol (113) with the appropriately activated R 28 - χ5 or R30 group yields compound (114). In this step, the nitrogen is readily acylated or sulfonylated leaving the alcohol untouched, since it is more nucleophilic. For example, 4-(2-hydroxyethyl)piperidine, may be readilly protected on the nitrogen exclusively with a carbamate (X 5 = -CO-0-) such as a BOC group by simply reacting with BOC 2 O and triethylamine in DMF (M.E. Duggan, G.D. Hartman, N. Khle European Patent Application 512,829, published November 11 , 1992). Reaction of the aminoalcohol with alkyl- or arylchloroformates in the presence of an acid scavenger such as triethylamine at O °C also yields carbamates selectively (W. Wiegreve, et al., Helv. Chim. Ada, 1974, 57, 301 ; F. Schneider, Helv. Chim. Ada, 1974, 57, 434; S. Umezawa, J. Antibiotics, 1974, 27, 997). Amides (X 9 = -CO-) may be made by simply stirring the amino alcohol with an appropriate ester (Y. Yamamoto, et al. Agri. Bio. Chem. 1985, 49, 1761) or with an acid chloride in the presence of an acid scavenger such as triethylamine at O °C (P.E. Sonnet et al., J. Org. Chem. 1980, 45, 3137) or with a carboxylic acid anhydride (D. A. Evans, J.M. Takacs Tet. Lett. 1980, 21, 4233; F.A. Davis, L.C. Vishwakarma Tet. Lett. 1985, 26, 3539). Sulfonamides (X 5 = -S0 2 -) may be made by stirring the aminoalcohol with a sulfonylchloride in the presence of an acid scavenger such as triethylamine at O °C (H. Takahashi, et al. Chem. Pharm. Bull., 1991, 39, 260). Ureas (X 5 = -CONH-) may be made by stirring the aminoalcohol with an isocyanate R 8 N=C=0 (J.W. Kobzina, U.S. Patent number 4,065291 , issued December 27, 1977). Ureas (X 9 = -CONH-) may also be made by stirring the aminoalcohol with a carbamyl chloride R 28 NR 11a COCI in the presence of an acid scavenger such as triethylamine at O °C (G. Hilgetag, AA. Martini "Preparative Organic Chemistry" John Wiley and Sons, New York, 1972, 469). The R 30 groups may be also attached to the amino group by the methods discussed above and previously using the appropriate starting material. Once again, all of these reactions selectively attach functionality to the nitrogen, but not to the alcohol. The alcohol may be converted to a leaving group such as a tosylate or bromide or a NR 11 a group as shown by methods previously discussed elsewhere in this application. These radicals then may be attached to the L 1 or L 2 group to yield the side-chain described by A, subheading (tt) or (uu) by the same methods previously described in this application. In addition, the entire side-chain need not be elaborated before coupling it to the L 1 or L 2 group, but can be partially assembled as shown in the following discussion. Aminoalcohol (113) is selectively protected (for example, with a BOC group as described above) to yield (118) and then is coupled to the L 1 or L 2 group. Deprotection and then coupling with the activated X 9 -R 28 or R 30 groups as previously described yields the side-chain described by A, subheading (tt) or (uu). Conversion of (118) to amine (119) by methods described previously followed by coupling to the L 1 or L 2 group, deprotection, and finally coupling with the activated X 9 or R 30 groups as previously described yields the side- chain described by A, subheading (tt) and (uu) wherein L 1 = -CONR 11a -. Compounds represented by A, subheading (w) to (ccc) may be synthesized by the procedures already described in this application from the appropriate starting material and by methods familiar to one skilled in the art. The examples in Schemes 22 and 23 describe cases wherein v=2, or the heterocycles are all piperidines. For the pyrrolidine cases (v= 1 ), the corresponding reactions can be performed on proline or betaproline (H. Yuki, Y. Okamoto, Y. Kobayashi J. Polym Sci. Polym. Chem. Ed. 1979, 17, 3867). Some starting materials, such as proline, are available in optically active form and the chirality can be carried through to the final product. If starting materials are racemic, then a resolution must be performed somewhere in the synthesis to obtain the product in enantiomeric form. Resolving methods include crystallization or chromatographic separation on a chiral column. Schemes 24 and 25 show two ways in which the bottom phenyl ring of the molecules is attached. The first way as shown in Scheme 24 involves first, the connecting of the two phenyl rings together, in this case to form a biphenyl. This is then followed by the elaboration of A and finishing off with the elaboration of the acidic moiety, namely R 13 . It is also possible to elaborate R 13 first, followed by A. It is also possible to partially elaborate A (we will refer to the precursor of A as A'), then R 13 and then finish with the final elaboration of A. All of these manipulations in relation to A have been previously described. The second way exemplified in Scheme 25 involves the alkylation of a benzyl onto the imidazole, followed by elaboration of A. Subsequent coupling of the second phenyl ring yields in this case a biphenyl system. Finally, the R 13 group is elaborated into its final form. Here as above, the A group does not have to be fully elaborated and its full elaboration can be put off to a later stage, depending on the compatability of the various groups in the molecule. Scheme 24 126 125 124 Scheme 25 136 More specifically, we see in Scheme 24, that alkylation onto imidazole (120) (disclosed in U.S. PATENT 5,138,069, U.S. Application 07/544557) with a benzyl halide, tosylate, mesylate, etc. in an inert solvent such as DMF in the presence of an acid scavenger such as K2CO3 yields benzylimidazole (121 ). The A' group can be fulther elaborated by methods familiar to one skilled in the art into (CH 2 )nCOOH to yield (2) which was seen eariier. However, for our present purposes, A' can equal C0 2 Me or compound (122). This ester group directs alkylation regioselectively as shown in U.S. Application 07/544557 . Suzuki coupling of bromobenzene (122) with boronic acid (123) (N. Miyaura, T. Yanagi, A. Suzuki, op. cit.) yields biphenyl (124). Note, that for simplicity, the phenylboronic acid (123) is unsubstituted but may be substituted with R 2 and R 3 groups as specified in the scope of this application. The synthesis of boronic acid (123) is shown in Scheme 26 and will be discussed later. Saponification of the ester yields (125). Removal of the t-butyl group with trifluoroacetic acid yie.lds carboxylic acid-sulfonamide (126). Alkylation with bromide (127) in an inert solvent such as DMF in the presence of an acid scavenger such as K2CO3 yields ester (128). Sometimes, alkylation occurs both on the carboxylic acid and the sulfonamide. These two compounds are readily separated by chromatography. Finally acylation yields (129) as either a sulfonylcarbamate, acylsulfonamide, or sulfonylurea, depending on the acylating agent. For example, acylating with an alkyl- or arylchloroformate in an inert solvent such as THF or pyridine with or without the use of an activating agent such as 4- (N.N-dimethylamino)pyridine yields a sulfonylcarbamate (SO2-NH-CO2R 10 ). Doing the same with an acid chloride yields an acylsulfonamide (SO2-NH- COR 10 ). Reacting sulfonamide (128) with an isocyanate yields a sulfonylurea (SO2-NH-CO-NHR 9 ) (Canadian patent application 2,058,198, published 1992/07/05, Hoechst Aktiengesellschaft). Finally, substitution with R 9 -X where X is a leaving group yields a differently substituted sulfonamide (SO2- NH-R 9 ), these substitution reactions being either SN2 or aromatic or heteroaromatic substitution reactions, all of which are familiar to one skilled in the art. The synthesis of these and other carboxylic acid isosteres is summarized in a Merck patent application (European Patent Application 400974, December 5, 1990). In Scheme 25, we see that regioselective alkylation with the brominated analog of (130) onto the imidazole aldehyde yields benzylimidazole (131 ). The aldehyde directs regioselective alkylation (U.S. Application 07/544557). Grignard additon followed by oxidation of the intermediate alcohol yields ketone (132). Deprotonation with LDA followed by alkylation with benzylbromide (133) yields (134) in which the A group is fully elaborated. Attachment of the bottom phenyl ring via Suzuki coupling (N. Miyaura, T. Yanagi, A. Suzuki, op. cit.) yields biphenyl (135). Cleavage of the t-butyl group with TFA and acylation yields sulfonylcarbamate (136). In a similar fashion, the acylsulfonamide, sulfonylurea, and differently substituted sulfonamide could have been made as described in the previous paragraph. Other carboxylic acid isosteres within the scope of R 3 can be substituted in place of the ones discussed in Schemes 24.and 25 using the Suzuki aryl coupling methodology or any other coupling strategy discussed previously employing the appropriate starting materials and the synthetic strategies outlined in Schemes 24 and 25. Again, the syntheses of these acid isosteres is discussed in a Merck patent application (European Patent Application 400974, December 5, 1990). In the case where there is no bottom phenyl ring and therefore the imidazole is substituted by only a benzyl group and the benzyl group contains an acid isostere (R 1 ), then the synthetic strategy follows that of the biphenyl case with manipulations being performed in a similar fashion at A' and R 1 (instead of R 13 ). The β-ketoamides listed in Table 3 can be prepared following the procedures outlined in Scheme 25a. Addition of vinyl Grignard to the benzylimidazole followed by oxidation of the intermediate alcohol yields the vinyl ketone. Michael addition of primary amine followed by acylation of the secondary amine with acyl chloride produces the β-ketoamide. Suzuki coupling of the aryl bromide with the boronic acid gives the biphenyl. The acylsulfonamides, sulfonylurea and sulfonyl carbamates can be made in a similar fashion as described previously in this section. One may alkylate the imidazole nitrogen with a preformed diaryl piece, such as the biphenyl moiety (37) shown in Scheme 26. Scheme 26 Sulfonamidoboronic acids (140) may be prepared by ortho-lithiation of sulfonamide (139), followed by treatment with triisopropyl borate and hydrolysis, as shown in Scheme 27. The biphenyl sulfonamides (142) may be prepared as described in EP479.479 or by aromatic coupling chemistry (Suzuki coupling), shown in Scheme 27. Scheme 27 139 140 141 142 143 The imidazole precursors shown in Scheme 26 and elsewhere in this application may be prepared as described in U.S. patents 5,137,902 and 5,138,069, in PCT U.S. Application 90/03683 and in European Application EP465.368 (see also Australian Patent AU-A-80163/91 ) and in U. S. Application 07/544557, which are hereby incorporated by reference. Phenylimidazoles useful in preparing compounds of the Formula (I) where R 8 is phenyl can be obtained as shown in Scheme 28. Thus, phenylboronic acids, available using standard methods, can be coupled with iodoimidazoles (144) to yield phenylimidazoles (145). The boronic acids may contain substituents on the phenyl ring so as to allow convenient preparation of the compounds of the present invention where R 8 is a substituted phenyl. Scheme 28 144 145 Compounds where L 3 is -O2C- may be synthesized as shown in Scheme 29. Scheme 29 93 146 Thus, alcohol (93) may be acylated by a variety of methods familair to one skilled in the art to yield ester (146) where the R group represents any of the side-chains disclosed in A (ee) through (ss) and (vv), (ww), (bbb), and (ccc) in the scope of this application. These methods include the Schotten-Baumann reaction, carbodiimide coupling, use of carbonyldiimidazole, etc. (for a summary on esterification reactions, see J. March Advanced Organic Chemistry, 3rd ed., New York: John Wiley and Sons, pp. 348-351), which have been discussed previously. And again as discussed previously, the side-chain -O2C-R may be acylated as a whole completed unit or piece-wise depending on whether X 2 , X 3 , X 4 , and X 5 may be formed via condensation reactions. Aryloxyacetylimidazoles of Formula (I) such as (150) can be prepared as exemplified in Scheme 30. Thus, methyl, ketone (67) may be converted to the corresponding silyl enol ether using e.g. trimethylsilyl triflate/triethylamine. Bromination with NBS, followed by reaction with phenol (148) provides the phenoxyacetylimidazole (149), which may be converted to compounds of Formula (I) as described in Scheme 25. Scheme 30 The compounds of this invention and their preparation can be understood further by the following examples which do not constitute a limitationof the invention. In these examples, unless otherwise indicated, all temperatures are in degrees centigrade and parts and percentages are by weight. Preparation of 4-[(5-(2-benzoy0benzyloxycarbonyl-4-ethyl-2-n-propylimidazol- 1-yπmethyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonylbiphenyl. potassium salt- Part A. Preparation of 1-Bromo-4-bromomethyl-3-fluorobenzene. 1-Bromo-3-fluoro-4-methylbenzene (28.37 g, 0.15 mol, 1 eq), N- bromosuccinimide (26.72 g, 0.15 mol, 1 eq), azobisisobutyronitrile (1.44 g) and carbon tetrachloride (500 mL) were mixed and refluxed overnight. The mixture was filtered and washed with water (3 X 300 mL). The organic layer was dried (MgS04), and the solvent removed in vacuo to yield 37.88 g of an oil (75% product by NMR). NMR (CDCI3) δ 4.45 (s, 2H). This material was used in the subsequent step without further purification. Part B. Preparation of 1 -f(4-Bromo-2-fluorophenvπmethyl]-5-carbomethoxy-4- ethyl-2-n-propylimidazole. 5-Carbomethoxy-4-ethyl-2-n-propylimidazole (U.S. Patent 5,137,902) (10.62 g, 54 mmol, 1 eq), 1-bromo-4-bromomethyl-3-fluorobenzene (19.58 g, 54 mmol, 1 eq), potassium carbonate (7.48 g, 54 mmol, 1 eq), and DMF (200 mL) were mixed and stirred overnight at room temperature. Ethyl acetate was added (500 mL) and the mixture was washed with water (3 X 300 mL). The ethyl acetate layer was dried (MgSθ4), and the solvent removed in vacuo to yield 25.42 g of an oil. Flash chromatography in 75:25 to 65:35 hexanes/ethyl acetate yielded 13.65 g of product as an amber oil. NMR (CDCI3) δ 7.35-7.22 (m, 1 H); 7.22-7.10 (m, 1 H); 6.45 (t, 1 H, J=7Hz); 5.49 (s, 2H); 3.78 (s, 3H); 2.90 (q, 2H, J=7Hz); 2.59 (t, 2H, J=7Hz); 1.70 (t of q, 2H, J=7,7Hz); 1.35- 1.15 (m, 3H); 0.95 (t, 3H, J=7Hz). Part C. Preparation of 2-(t-butylamino)sulfonylphenyl boronic acid To a 0°C solution of 34.0 g (0.16 mol) of benzene-N-(t- butyl)sulfonamide in 500 mL of THF under N2 was added 160 mL (0.36 mol) of 2.25 M n-butyllithium in hexane over 35 min., keeping the temperature between 0-2°C. The reaction mixture was allowed to warm to room temperature over 1.5 h, during which time a thick precipitate formed. Triisopropylborate (46 mL, 0.20 mol) was added, keeping the temperature below 35°C. After 1 h, the reaction mixture was cooled, 1 N HCI (260 mL)was added, and the mixture was stirred 30 min. .After diluting with 520 mL of water, the mixture was extracted with 3x 400 mL of ether. The combined organic extracts were extracted with 3x 200 mL of 1 N NaOH, and the aqueous extracts were acidified to pH 1 with 6 N HCI, then extracted with 3x 250 mL of ether. The ether extracts were washed with 250 mL of brine, dried over MgSθ4 and the solvents were removed in vacuo to yield 45 g of a thick oil. After addition of toluene (45 mL), the mixture was agitated for 1 h on the rotary evaporator. A small quantity of solid formed, which was used to induce partial solidification of the remaining crude product. Additional toluene (150 mL) was added, and the mixture was reduced to 1/2 volume in vacuo, keeping the temperature from 0-10°C. The resulting precipitate was collected and washed with hexane, then dried under vacuum to give 24.6 g ( 60%) of the title compound as white crystals, m.p. 118-119°C. 1 H NMR (CDCI3): δ 1.18 (s, 9H, CH3); 5.13 (s, 1 H, NH), 6.29 (br s, 2H, OH); 7.53 (m, 2H, ArH); 7.82 (d, 1 H, ArH); 8.00 ( d, 1 H, ArH). Part P. Preparation of 2'- ( N-t-butvπsulfonamido-4-[(5-carbomethoxy-4-ethyl- 2-n-propylimidazol-1 -v methyl]-3-fluorobiDhenyl. 1-[(4-Bromo-2-fluorophenyl)methyl]-5-carbomethoxy-4-ethyl-2-n- propylimidazole (5.00 g, 13 mmol, 1 eq) was dissolved in toluene (25 mL) and added to a suspension of potassium carbonate (3.61 g, 26 mmol, 2 eq), tetrabutylammonium bromide (0.42 g, 1.3 mmol, 0.1 eq), 2-(t- butylamino)sulfonylphenyl boronic acid (5.03 g, 20 mmol, 1.5 eq) in toluene (25 mL). Water (10 mL) was then added followed tetrakistriphenylphosphine palladium (0) (0.75 g, 0.65 mmol, 0.05 eq). The mixture was slowly warmed to reflux temperature. After 16 hours, the reaction was worked up by adding water and extracting with methylene chloride (3X). The methylene chloride layers were combined and rinsed with brine (1 X). The organic layer was dried (MgS04), and the solvent removed in vacuo to yield 9.69 g of an amber oil Flash chromatography in 75:25 to 1 :1 hexanes/ethyl acetate yielded 5.89 g of an amber oil. NMR (CDCI3) δ 8.06 (d, 1 H, J=8Hz); 7.47 (t, 1 H, J=8Hz); 7.40 (t, 1 H, J=8Hz); 7.30-7.15 (m, 2H); 7.08 (d, 1 H, J=8Hz); 6.58 (t, 1 H, J=7Hz); 5.53 (s, 2H); 3.70 (s, 3H); 3.60 (s, 1 H); 2.83 (q, 2H, J=7Hz); 2.57 (t, 2H, J=7Hz); 1.65 (t of q, 2H, J=7,7 Hz); 1.20-1.10 (m, 3H); 0.91 (s, 9H); 0.87 (t, 3H, J=7Hz). Part E. Preparation of 2'-(N-t-butvnsulfonamido-4-f(5-carboxv-4-ethvl-2-n- propvlimidazol-1-yhmethyl]-3-fluorobiphenvl. 2'-(N-t-butyl)sulfonamido-4-[(5-carbomethoxy-4-ethyl-2-n- propylimidazol-1 -yl)methyl]-3-fluorobiphenyl (5.89 g, 11.4 mmol, 1 eq), 10 N NaOH (11.42 mL, 114 mmol, 10 eq), THF (25 mL), and methanol (enough to make a solution) were mixed and heated at 50 °C overnight. The reaction was worked up by adding water and removing the organic solvents in vacuo on a rotary evaporator. Methanol was added and the pH was adjusted to about 2 with concentrated HCI. The methanol was removed in vacuo and solids precipitated from the water. These solids were filtered, rinsed with ether and pumped under high vacuum to yield 4.45 g of a light yellow product: m.p. 223.5-224.5 °C. The solvent was further reduced from the filtrate yielding more product as a second crop: 1.13 g, m.p. 223.0-224.0 °C. NMR (DMSO-d 6 ) δ 8.01 (d, 1 H, J=7Hz); 7.58 (m, 2H); 7.35-7.20 (m, 2H); 7.14 (d, 1 H, J=7Hz); 6.94 (t, 1 H, J=7Hz); 6.80 (s, 1 H): 5.79 (s, 2H); 3.05-2.80 (m, 4H): 1.66 (t of q, 2H, J=7,7 Hz); 1/23 (t, 3H, J=7Hz); 0.95 (s, 9H); 0.88 (t, 3H, J=7Hz). Part F. Preparation of 4-[(5-Carboxy-4-ethyl-2-n-propylimidazol-1-yl)methyl|- 3-fluoro-2'-sulfonamidobiphenyl. 2 * -(N-t-Butyl)sulfonamido-4-[(5-carboxy-4-ethyl-2-n-propylimidazol-1 - yl)methyl]-3-fluorobiphenyl (5.58 g) and trifluoroacetic acid (TFA) (75 mL) were mixed and stirred at room temperature overnight. The TFA was removed in vacuo and the residue was dissolved in toluene. The toluene was removed in vacuo on a rotary evaporator and this procedure was repeated again to remove all traces of TFA. The residue was dissolved in ethyl acetate, dried (MgS04), and the solvent removed in vacuo Xo yield 6.92 g of an amber glass. NMR (DMSO-d 6 ) δ 8.10-7.95 (m, 1 H): 7.70-7.50 (m, 2H); 7.37 (s, 2H); 7.45-7.10 (m, 3H); 6.96 (t, 1 H, J=7Hz); 5.84 (s, 2H); 3.10-2.80 (m, 4H); 1.80-1.55 (m, 2H); 1.25 (t, 3H, J=7Hz); 0.91 (t, 3H, J=7Hz). The material was used without additional purification in the next step. Part G. Preparation of 4-f(5-(2-benzov0benzyloxycarbonyl-4-ethyl-2-n- propylimidazol-1-vπmethvn-3-fluoro-2'-sulfonamidobiDhenyl. 4-[(5-Carboxy-4-ethyl-2-n-propylimidazol-1-yl)methyl]-3-fluoro-2'- sulfonamidobiphenyl (6.92 g, 11 mmol, 1 eq), 2-benzoylbenzyl bromide (obtained through bromination of 2-methylbenzophenone by the procedure described in part A, except that the reaction was terminated after 1 h, and after work up, the unstable product was stored at 0° C) (7.57 g, 22 mmol, 2 eq), potasium carbonate (1.52 g, 11 mmol, 1 eq) and DMF (75 mL) were mixed and stirred overnight. The reaction was worked up as described in Part B. Flash chromatography in 75:25 to 0:100 hexanes/ethyl acetate yielded 2.41 g of an amber glass. FAB MS detects M++H = 446. Part H. Preparation of 4-f(5-(2-benzovπbenzyloxycarbonyl-4-ethyl-2-n- propylimidazol-1-vπmethvn-3-fluoro-2'- isoamyloxycarbonylaminosulfonylbiphenyl. potassium salt. 4-[(5-(2-Benzoyl)benzyloxycarbonyl-4-ethyl-2-n-propylimidazol-1- yl)methyl]-3-fluoro-2'-sulfonamidobiphenyl (2.41 g, 3.77 mmol, 1 eq), 4-N.N- dimethylaminopyridine (1.84g, 15.1 mmol, 4 eq), isoamyl chloroformate (9.87 g, 15.1 mmol, 4 eq), pyridine (11 mL) and methylene chloride (50 mL) were mixed and stirred at room temperature. After 48 h, the reaction was complete. Methylene chloride was added and the mixture was rinsed with water (1X), 10% citric acid (2X), and brine (1X). The organic layer was seperated, dried (MgS04), and the solvent removed in vacuo to yield an amber oil. Flash chromatography in 1 :1 hexanes/ethyl acetate to 100% ethyl acetate yielded 1.26 g of product as a tan colored glass. The product was further titrated with 0.09 M KOH and the water removed in vacuo followed by azeotroping with isopropanol to yield 1.20 g of an amber glass. NMR (CDCI3) δ 8.07 (d, 1H, J=8Hz); 7.72 (d, 2H, J=8Hz); 7.60-7.00 (m, 12H0; 6.36 (t, 1H, J=8Hz); 5.40 (s, 2H); 5.34 (s, 2H); 3.71 (t, ' 2H, J=7Hz); 2.64 (q, 2H, J=7Hz); 2.56 (t, 2H, J=7Hz); 1.66 (t of q, 2H, J=7,7Hz); 1.40 (m, 1H); 1.22 (q, 2H, J=7Hz); 1.07 (t, 3H, J=7Hz); 0.91 (t, 3H, J=7Hz); 0.71 (d, 6H, J=7Hz). Anal, calcd. for C42H44FN 3 OS*(H 2 0)o.5: C, 62.98; H, 5.54; F, 2.37; N, 5.25; S, 4.00. Found: C, 62.85; H, 5.54; F, 2.33; N, 5.09; S, 3.79. Preparation of 4-r(5-(2-benzovnbenzvloxvcarbonvl-4-ethvl-2-n-Droovlimida7ol- 1 -yhmethvH-3-fluoro-2'-M H-tetrazol-5-vnbiphenvl. Part A. Preparation of 3-fluoro-4-methvl-2'-CN-triphenvlmethvl-1 H-tetrazol-5- yPbip eπyl. 4-Bromo-2-fluorotoluene (5.00 g, 26 mmol, 1 eq), 2-(N-triphenylmethyl- 1 H-tetrazol-5-yl)benzeneboronic acid (U.S. Patent 5,130,439) (14.29g, 26 mmol, 1 eq), tetrakistriphenylphosphinepalladium (0) (1.53 g, 1.3 mmol, 0.05 eq), tetrabutylammonium bromide (0.42 g, 1.3 mmol, 0.05 eq), 2M sodium carbonate (28.99 mL, 58 mmol, 2.23 eq) and toluene (200 mL) were mixed and refluxed for 4 hours. The reaction was worked up as in example 1 , part D to yield 11.98 g of an amber glass. The glass was dissolved in ethyl acetate (25 mL) and triturated with ether to yield 6.04 g of white solid product. The filtrate was concentrated and flash chromatographed in 9:1 hexanes/ethyl acetate to yield a further 3.72 g of white solid product. NMR (CDCI3) δ 8.00- 7.85 (m, 1H); 7.55-7.40 (m, 2H); 7.40-7.10 (m, 10H); 7.00-6.70 (m, 9H); 2.18 (S, 3H). Part B. Preparation of 4-bromomethyl-3-fluoro-2'-(N-triphenylmethyl-1 H- tetrazol-5-vπbiPhenyl. 3-Fluoro-4-methyl-2'-(N-triphenylmethyl-1 H-tetrazol-5-yl)biphenyl (6.00 g, 12 mmol) was brominated by the procedure described in example 1 , part A to yield 7.45 g of an amber glass. NMR (CDCI 3 ) δ 4.39 (-CH 2 Br). Part C. Preparation of 1 -[(3-fluoro-2'-(N-triphenylmethyl-1 H-tetrazol-5- vπbiphenvπmethyl]-5-carbomethoxy-4-ethyl-2-n-propylimidazole. 4-bromomethyl-3-fluoro-2'-(N-triphenylmethyl-1 H-tetrazol-5-yl)biphenyl (7.45 g, 11.0 mmol, 1 eq) was alkylated onto 5-carbomethoxy-4-ethyl-2-n- propylimidazole (2/16 g, 11.0 mmol, 1 eq) by the procedure described in Example 1 , part B to yield after chromatography 2.53 g of an amber glass. NMR (CDCI3) δ 8.00-7.80 (m, 1HJ.; 7.60-7.40 (m, 2H); 7.40-7.15 (m, 10H); 7.05-6.70 (m, 8H); 6.43 (t, 1 H, 5.47 (s, 2H); 3.71 (s, 3H); 2.91 (q, 2H, J=7Hz); 2.48 (t, 2H, J=7Hz); 1.75-1.55 (m, 2H); 1.26 (t, 3H, J=7Hz); 0.87 (t, 3H, J=7Hz). Part P. Preparation of 1-[(3-fluoro-2'-M H-tetrazol-5-vnbiphenvnmethvl]-5- carboxv-4-ethvl-2-n-propvlimidazole. 1 -[(3-Fluoro-2'-(N-triphenylmethyl-1 H-tetrazol-5-yl)biphenyl)methyl]-5- carbomethoxy-4-ethyl-2-n-propylimidazole (2.02 g, 2.92 mmol, 1 eq), 1.000 N NaOH (5.85 mL, 5.85 mmol, 2 eq), THF (10 mL) and methanol (enough to solublize the mixture) were mixed and stirred at room temperature overnight. The reaction was incomplete and so another 2 equivalents of 1.000 N NaOH were added and the mixture stirred for an additional 4 hours. The reaction was istill ncomplete and so another 4 equivalents of 10 N NaOH were added and the mixture stirred overnight at room temperature. The reaction was worked up by adding water and removing the organic solvents in vacuo. The remaining aqueous mixture was rinsed with ether (3X). Ethyl acetate was added to the aqueous mixture and the pH was adjusted to 2-3 with cone. HCI. The layers were seperated and the aqueous layer was extracted (2X) with ethyl acetate. The ethyl acetate layers were combined, dried (MgSθ4), and the solvent removed in vacuo to yield a yellow glass. The glass was stirred in ether to triturate 1.19 g of solid product. NMR shows that both the triphenylmethyl group and the methyl ester had been cleaved. NMR (DMSO- d 6 ) δ 7.80-7.40 (m, 4H); 7.00 (d, 1 H, J=10 Hz); 6.87 (d, 1 H, J=8Hz); 6.62 (t, 1 H, J=8Hz); 5.64 (s, 2H); 2.83 (q, 2H, J=7Hz); 2.67 (t, 2H, J=7Hz); 1.56 (t of q, 2H, J=7,7Hz); 1.15 (t, 3H, J=7Hz); 0.84 (t, 3H, J=7Hz). FAB MS: (M++H) = 435. Part E. Preparation of t-r(3-fluoro-2'-(N-triphenvlmethvl-1 H-tetrazol-5- yhbiphenvhmethvπ-5-carboxv-4-ethyl-2-n-propylimidazole. 1-[(3-Fluoro-2'-(1 H-tetrazol-5-yl)biphenyl)methyl]-5-carboxy-4-ethyl-2- n-propylimidazole (960 mg, 2.21 mmol, 1 eq), triethylamine (0.34 mL, 2.43 mmol, 1.1 eq), triphenylmethyl chloride (678 mg, 2.43 mmol, 1.1 eq), and methylene chloride (10 mL) were mixed and stirred at room temperature. After 4 hours, the reaction was worked up by adding water and seperating the layers, The organic layer was dried (MgSθ4), and the solvent removed in vacuo to yield 1.48 g of a white glass. Flash chromatography in 1 :1 hexanes/ethyl acetate to 100 % ethyl acetate to 75:25 ethyl acetate/isopropanol to yield 1.01 g of product as a white glass. NMR (CDCI3) δ 7.80-7.60 (m, 1 H); 7.50-7.05 (m, 12H); 6.94 (d, 6H, J=8Hz); 6.80-6.40 (m, 3H); 5.70-5.30 (m, 2H); 2.90-2.70 (m, 2H); 2.40-2.10 (m, 2H); 1.50 (m, 2H); 1.10-0.80 (m, 3H); 0.75-0.40 (m, 3H). Part F. Preparation of 4-[(5-(2-benzovπbenzyloxycarbonyl-4-ethyl-2-n- propylimidazol-1-y0methyl]-3-fluoro-2 N-triphenylmethyl-1 H-tetrazol-5- yDbiphenyl. 1-[(3-Fluoro-2'-(N-triphenylmethyl-1 H-tetrazol-5-yl)biphenyl)methyl]-5- carboxy-4-ethyl-2-n-propylimidazole (0.47 g, 0.694 mmol) was alkylated with 2-benzoyl benzyl bromide by the procedure described in example 1 , part G to yield after flash chromatography in 75:25 to 1 :1 to 0:100 hexanes/ethyl acetate 440 mg of an amorphous white product. NMR (CDCI3) δ 7.95-7.85 (m, 1 H); 7.75 (d, 2H, J=8Hz); 7.60-7.15 (m, 19 H); 6.94 (d, 6H, J=8Hz); 6.90-6.70 (m, 2H); 6.39 (t, 1 H, J=8Hz); 5.38 (s, 2H); 5.35 (s, 2H); 2.77 (q, 2H, J=7Hz); 2.41 (t, 2H, J=7Hz); 1.75-1.50 (m, 2H); 1.14 (t, 3H, J=7Hz); 0.84 (t, 3H, J=7Hz). Part G. Preparation of 4-[(5-(2-benzov0benzyloxycarbonyl-4-ethyl-2-n- propylimidazol-1-yπmethyl]-3-fluoro-2'-(1 H-tetrazol-5-vπbiphenyl. 4-[(5-(2-Benzoyl)benzyloxycarbonyl-4-ethyl-2-n-propylimidazol-1- yl)methyl]-3-fluoro-2'-(N-triphenylmethyl-1 H-tetrazol-5-yl)biphenyl (440 mg) and methanol (25 mL) were mixed and refluxed under nitrogen for 3 hours. Silica gel was added and the solvent removed in vacuo. The residue was added to a flash chromatography column and quickly chromatographed in 1 :1 hexanes/ethyl acetate to 80:20 chloroform/methanol to yield 280 mg of product as an off-white glass. NMR (CDCI 3 ) δ 7.83 (d, 1 H, J=7Hz); 7.68 (d, 2H, J=7Hz); 7.60-7.10 (m, 10H); 6.80-6.60 (m, 2H); 6.27 (t, 1 H, J=7Hz); 5.30 (s, 4H); 2.50 (m, 2H); 2.33 (t, 2H, J=7Hz); 1.54 (t of q, 2H, J=7,7 Hz); 0.95-0.60 (m, 6H). Anal, calcd. for C37H33FN6O3: C, 67.77; H, 5.53; F, 2.90; N, 12.82. Found: C, 67.73; H, 5.15; F, 2.76; N, 12.62. Pre aration Of 1 -((2 , -((n-BμtylP^ycarbQnyl-amiηQ)sμlfpnyl)-3-flμρrp-(1 ,1 '- biphenvn-4-vnmethvn-4-ethvl-5-(2-f2-phenoxvphenvnethvlcarbonvn-2-propvl- 1 H-imidazole. Part A: Preparation of 1-(2-fluoro-4-iodobenzvπ-4-ethyl-2-propyl-1 H- imidazole-5-carboxaldehvde A solution of 2-fluoro-4-iodotoluene (47.28 g, 0.20 mol), N- bromosuccinamide ( 37.64 g, 0.21 mol) and azobisisobutyronitrile ( 3.65 g, 0.02 mol) in CCI4 (200 mL) was refluxed under N2 overnight. The mixture was cooled, the solid was filtered off and washed with CCI4. The filtrate was concentrated. The precipitated formed was filtered and washed with hexane to give 13.92 g of 86% pure benzyl bromide. The mother liquid was concentrated to give 48.88 g of 60% pure benzyl bromide. Both fractions were used without further purification in the next step. 4-Ethyl-2-propyl-1 H-imidazole-5-carboxaldehyde (6.32 g, 38.0 mmol), potassium carbonate (10.57 g, 76.5 mmol) , and 2-fluoro-4-iodobenzyl bromide (13.90 g of 86%, 38.0 mmol) were added together with 50 mL of DMF. The reaction mixture was stirred at room temperature overnight under N2- The solvent was removed in vacuo and the residue was partitioned between EtOAc and H2O. The two layers were separated. The aqueous layer was extracted with EtOAc. The combined organic mixture was washed with H2O and brine, dried over MgSθ4 and concentrated. The crude product mixture was purified by flash chromatography (silica gel, 30-50% EtOAc/hexane) to yield 10.63 g orange oil (70%). MS m/e 401.0, [M+H]+; 1 H NMR ( 300 MHz, CDCI3): δ 0.95 (t, 3H, CH3), 1.32 (t, 3H, CH3), 1.70 (m, 2H, CH2), 2.60 (m, 2H, CH2), 2.82 (q, 2H, CH2), 5.52 (s, 2H, CH2Ar), 6.42 (t, 1 H, ArH), 7.38 (d, 1 H, ArH), 7.42 (d, 1 H, ArH), 9.73 (s, 1 H, CHO). Part B: Preparation of 1-(2-fluoro-4-iodobenzvπ-5-acetyl-4-ethyl-2-propyl-1 H- imidazole To a solution of 1-(2-fluoro-4-iodobenzyl)-4-ethyl-2-propyl-1 H-imidazole-5- carboxaldehyde (16.52 g, 41.3 mmol) in THF (100 mL) was added methylmagnesium bromide (44.0 mL of 1.4/M in toluene/THF, 61.6 mmol) over 30 minutes. The reaction mixture was stirred at room temperature for 1 ,5h. It was then quenched with 100 mL of 1 N aqueous HCI. The mixture was extracted with CH2CI2, the organic solution was washed with H2O and brine, dried over MgSθ4, and concentrated to a yellow oil (16.87 g). The yellow oil was dissolved in 400 mL of CH2CI2, and Manganese(IV) oxide (70.50 g, 811 mmol) was added. The mixture was refluxed under N2 overnight. The mixture was cooled. It was then filtered through celite and washed with CH2CI2. The CH2CI2 solution was concentrated and chromatographed on silica gel with 50% EtOAc/hexane and 10% MeOH/CH2Cl2 to give 4.70 g of the desired product and 6.87 g of the alcohol. MS m/e 415.0, [M+H]+; 1 H NMR ( 300 MHz, CDCI3): δ 0.98 (t, 3H, CH3), 1.35 (t, 3H, CH3), 1.68 (m, 2H, CH2), 2.42 (s, 3H, CH3), 2.58 (m, 2H, CH2), 2.92 (q, 2H, CH2), 5.45 (s, 2H, CH2Ar), 6.28 (t, 1H, ArH), 7.35 (d, 1 H, ArH), 7.42 (d, 1H, ArH). Part C: Preparation of o-phenoxvbenzvl alcohol To a solution of o-phenoxybenzoic acid (19.0 g, 88.7 mmol) in THF (100 mL) at 0°C under N2 was added BH3 HF (133 mL, 1.0M in THF) over a period of 1 h, keeping the temperature below 5°C. The reaction mixture was then stirred at room temperature for 2h. It was quenched with H2O, then 1 N aqueous HCI. The two layers were separated. The aqueous layer was extracted with EtOAc. The combined organic mixture was washed with brine, dried over MgSO, and concentrated to a light yellow oil(16.9 g). The crude product was used in the next step without further purification. MS m/e 183.1 , [M+H-H2θ]+; 1 H NMR ( 300 MHz, CDCI3): δ 2.08 (t, 1 H, OH), 4.76 (d, 2H, CH2Ar), 6.82-7.48 (m, 9H, ArH). Part D: Preparation of o-phenoxybenzyl iodide To a solution of o-phenoxybenzyl alcohol (5.0 g, 25 mmol) and triethylamine (10.4 mL, 75 mmol) in CH2CI2 (50 mL) at 0°C was added methanesulfonyl chloride (3.9 mL, 50 mmol). The reaction mixture was stirred at 0°C for 1 h and then at room temperature for 3.5h. The mixture was washed H2O and brine. It was filtered through phase separator paper and concentrated to a yellow oil. The oil was then dissolved in 50 mL of acetone, and sodium iodide ( 7.5 g, 50 mmol) was then added. The mixture was stirred at room temperature overnight. Hexane was added to the mixture. The solid was filtered off. The filtrate was concentrated and chromatographed on silica gel with hexane to give 5.22 g of yellow oil. .MS m/e 183.1 , [M+H-HIJ+; H NMR ( 300 MHz, CDCl3):δ 4.52 (s, 2H, CH2Ar), 6.82-7.48 (m, 9H, ArH). Part E: Preparation of 1-(2-fluoro-4-iodobenzvπ-4-ethyl-5-(2-(2-phenoxy phenvhethylcarbonvπ-2-propyl-1 H-imidazole 1-(2-fluoro-4-iodobenzyl)-5-acetyl-4-ethyl-2-propyl-1 H-imidazole (5.52 g, 13.3 mmol) was dissolved in 50 mL of THF. The mixture was cooled at 0°C under N2 and lithium diisopropylamide (7.3 mL of 2M in THF, 14.6 mmol) was added. After stirred at 0°C for 15 minutes, a solution of o-phenoxybenzyl iodide (5.22 g, 16.8 mmol) in THF (15 mL) was added. The reaction mixture was warmed up to room temperature and stirred for 2h. The mixture was partitioned between EtOAc and H2O. The two layers were separated. The aqueous layer was extracted with EtOAc. The combined organic solution was washed with brine, dried over MgSθ4. It was concentrated and chromatographed on silica gel with 10-50% EtOAc/hexane to yield 2.35 g of the desired product. MS m/e 597.2, [M+H]+; IR (KBr): 1646 cm-1 for CO; 1 H NMR ( 300 MHz, CDCI3): δ 0.95 (t, 3H, CH3), 1.22 (t, 3H, CH3), 1.65 (m, 2H, CH2), 2.57 (m, 2H, CH2), 2.82 (q, 2H, CH2), 2.98 (m, 2H, CH2), 3.10 (m, 2H, CH2) 5.42 (s, 2H, CH2Ar), 6.22 (t, 1 H, ArH), 6.82 (d, 1 H, ArH), 6.90 (d, 2H, ArH), 7.02 (m, 2H, ArH), 7.18 (d, 1 H, ArH), 7.22 (m, 2H, ArH), 7.30 (m, 2H, ArH), 7.40 (d, 1 H, ArH). Part F: Preparation of 1-((2'-((t-butvlamino sulfonvn-3-fluoro-(1.1 '-biphenvn-4- yhmethvn-4-ethvl-5-(2-(2-phenoxvphenvnethvlcarbonvn-2-propvl-1 H- imidazQie 1-(2-fluoro-4-iodobenzyl)-4-ethyl-2-propyl-1 H-imidazole-5-phenoxyphenethyl ketone (2.35 g, 3.90 mmol), 2-(t-butylamino)sulfonylphenyl boronic acid (1.52 g, 5.85 mmol), and soduim carbonate (10 mL of 2M aqueous solution), and tetrabutylammonium bromide (65 mg, o.20 mmol) were added together with 50 mL of toluene. Tetrakis(triphenylphosphine) palladium(O) (0.23 g, 0.20 mmol) was added. The mixture was refluxed under N2 overnight. The solvent was removed in vacuo and the residue was partitioned between H2O and CH2CI2. The aqueous layer was extracted with CH2CI2, and the combined organic solution was washed with brine, dried over MgSθ4 and concentrated. The crude product was purified by flash column chromatography ( silica gel, 30% EtOAc/hexane) to give 1.92 g of light yellow foam (72%). MS m/e 682.5, [M+H]+; 1 H NMR ( 300 MHz, CDCI3): δ 0.96 (t, 3H, CH3), 0.98 (t, 9H, CH3), 1.27 (t, 3H, CH3), 1.69 (m, 2H, CH2), 2.60 (t, 2H, CH2), 2.85 (q, 2H, CH2), 2.97 (m, 2H, CH2), 3.13 (m, 2H, CH2), 3.58 (s, 1 H, NH), 5.57 (s, 2H, CH2Ar), 6.60 (t, 1 H, ArH), 6.86 (d, 1 H, ArH), 6.92 (d, 2H, ArH), 7.05 (d, 2H, ArH),7.16 (m, 2H, ArH), 7.26 (m,5H, ArH), 7.55 (m, 2H, ArH),8.16 (m, 1 H, ArH). Part G: Preparation of 1-((2'-(aminosulfonvn-3-fiuoro-M .1'-biphenvn-4- vπmethvπ-4-ethyl-5-(2-(2-phenoxyphenvπethylcarbonvπ-2-propyl-1 H- imidazole 1-((2'-((t-butylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4-yl)methyl)-4- ethyl-2-propyl-1 H-imidazole-5-phenoxyphenethyl ketone (1.92 g, 2.8 mmol) was refluxed with 15 mL of trifluoroacetic acid under N2 for 2 h. The solvent was removed in vacuo. The residue was dissolved in CH2CI2, and washed with aqueous NaHC03 and brine. The organic solution was filtered through phase separator paper and then concentrated to a light yellow foam (1.84 g). MS m/e 626.0, [M+H]+; 1 H NMR ( 300 MHz, CDCI3): δ 0.95 (t, 3H, CH3), 1.26 (t, 3H, CH3), 1.69 (m, 2H, CH2), 2.60 (t, 2H, CH2), 2.84 (q, 2H, CH2), 2.97 (m, 2H, CH2), 3.12 (m, 2H, CH2), 4.20 (s, 2H, NH2), 5.57 (s, 2H, CH2Ar), 6.65 (t, 1 H, ArH), 6.85 (d, 1 H, ArH), 6.92 (d, 2H, ArH), 7.01 -7.37 (m, 9H, ArH), 7.58 (m,2H, ArH), 8.15 (d, 1 H, ArH). Part H: Preparation of 1-((2'-((n-Butvloxvcarbonvlamino)sulfonvn-3-fluoro- (1.1'-biphenyn-4-vnmethvn-4-ethvl-5-(2-f2-phenoxvphenvnethvlcarbonvn-2- propvl-1 H-imidazole 1-((2'-(aminosulfonyl)-3-fluoro-(1 ,1 , -biphenyl)-4-yl)methyl)-4-ethyl-2- propyl-1 H-imidazole-5-phenoxyphenethyl ketone (1.84 g, 2.90 mmol) was dissolved in 50 mL of CH2CI2. To the mixture was added 4-N.N- dimethylaminopyridine (0.40 g, 3.19 mmol), pyridine (2 mL), and n-Butyl chloroformate (1.48 mL, 11.60 mmol). The reaction mixture was allowed to stir at room temperature under N2 for 98 h.. The mixture was washed with 10% aqueous citric acid and brine. The organic solution was filtered through phase separator paper and concentrated. It was then chromatographed on silica gel (eluted with 25-100% EtOAc/CH2Cl2 ) to give 1.48 g light yellow foam. MS m/e 725.0, [M+H]+; H NMR (300 MHz, CDCI3) δ 0.84 (t, 3H, CH3), 0.97 (t, 3H, CH3), 1.10-1.32 (m, 5H, CH3.CH2), 1.47 (m, 2H, CH2), 1.71 (m, 2H, CH2), 2.63 (t, 2H, CH2), 2.83 (q, 2H, CH2), 2.99 (m, 2H, CH2), 3.12 (m, 2H, CH2), 3.98 (t, 2H, OCH2), 5.58 (s, 2H, CH2Ar), 6.62 (t,1 H, ArH), 6.81-7.37 (m, 12H, ArH), 7.60 (m, 2H, ArH), 8.25 (d, 1 H, ArH). Example 4. Preoaration of 4-f(5-(2-trifluoromethylphenvhmethylaminocarbonyl-4-ethyl-2- π-prppylimidazpl-1-yl)methyl3-3-fluprp-2'- isoamvloxvcarbonvlaminosulfonvlbiphenvl. potassium salt Part A. Preparation of 4-[(5-.2-trifluoromethylphenylmethyl)aminocarbonyl-4- ethyl-2-n-propylimidazol-1-vπmethyl]-3-fluoro-2'-(N-t- butyπsulfonamidobiphenyl. A solution of (2-trifluoromethyl)benzylamine (0.22 mL, 1.6 mmol), dicyclohexylcarbodiimide (0.33 g, 1.6 mmol), and 1 -hydroxybenzotriazole hydrate (0.22 g, 1.6 mmol) in acetonitrile (30 mL) was stirred under N2 for 15 minutes. 2'-(N-t-butyl)sulfonamido-4-[(5-carboxy-4-ethyl-2-n-propylimidazol- 1 -yl)methyl]-3-fluorobiphenyl (0.75 g, 1.6 mmol) was then added and the reaction stirred at room temperature overnight. The reaction was filtered and the filtrate then evaporated. The residue was taken up in CH2CI2, washed with water, dried over MgS04, filtered and evaporated. The residue was then chromatographed with 50% ethyl acetate in hexane to yield 0.95 g of a white product. NMR (CDCI3) δ 8.09 (d, 1 H), 7.60-7.10 (m, 9H), 6.75 (t, 1 H), 6.04 (m, 1 H), 5.51 (m, 1 H), 4.67 (d, 2H), 2.63 (m, 2H), 2.53 (m, 2H), 1.60 (m, 2H), 1 ,18 (m, 3H), 0.90 (m, 12H) Part B. Preparation of 4-f(5-f2-trifluoromethvlphenvhmethvlaminocarbonvl-4- ethvl-2-n-propvlimidazol-1-vnmethvll-3-fluoro-2'- isoamvloxvcarbonvlaminosulfonvlbiphenvl. potassium salt. 4-[(5-(2-trifluoromethylphenyl)methylaminocarbonyl-4-ethyl-2-n- propylimidazol-1 -yl)methyl]-3-fluoro-2'-(N-t-butyl)sulfonamidobiphenyl was converted to product by using the methods of Example 1 , parts G and H. The reactions yielded 0.33 g of product. NMR (CDCI 3 ) δ 8.02 (d, 1 H), 7.64-7.05 (m, 9H), 6.56 (t, 1 H), 6.20 (m, 1 H), 5.33 (s, 2H), 4.65 (d, 2H), 3.77 (t, 2H), 2.67 (q, 2H), 2.54 (m, 2H), 1.65 (m, 2H), 1.40 (m, 1 H), 1.21 (m, 3H), 0.95 (t, 3H), 0.76 (d, 6H). Preparation of N-butyl. N-benzyl-2-(aminocarbonvπethvnylmethyl 4-ethyl-2- propyl-1-[[2'-(1 H-tetrazol-5-vπbiphenyl-4-yl1methyl]imidazole-5-carboxylate O-TBDMS = / Part A. Preparation of t-Butyldimethylsilyl proparαyl ether To a solution of 5.82 mL of propargyl alcohol in 20 mL of pyridine and 30 mL of CH2CI2 was added 0.122 g of DMAP and 16.88 g of TBDMSCI in a N2 atmosphere. After stirring 3 days, the reaction was poured into 100 mL of 1 N HCI, and diluted with CH2CI2. The layers were separated and the organic layer washed with 100 mL of 1 N HCI (2x), 10% NaHCθ3, H2O and brine and dried (MgSθ4). Filtration and concentration provided 15.07 g of an oil which was used without purification. H-NMR (CDCI3) δ 4.19 (s, 2H), 2.25 (s. 1 H), 0.80 (s, 9H), 0.03 (s, 6H). O-TBDMS HOOC- J Part B. Preparation of 4-(t-Butyldimethylsilyloxv 2-butvnoic acid To an ice-cold solution of 13.71 g t-butyldimethylsilyl propargyl ether in 160 mL anhydrous THF was added dropwise 35 mL EtMgBr (3M in Et2θ) in a N2 atmosphere. After completing the addition, the reaction was stirred 45 minutes at room temperature. Pellets of dry ice were then added slowly until the reaction became cold and carboxylate salt precipitated. Stirring at room temperature was continued overnight. The reaction was concentrated to dryness and the residue partitioned between H2O and Et2θ and the organic extract discarded. The aqueous solution was acidified to pH 2 with 6N HCI and immediately extracted with EtOAc. The organic layer was washed with 10% NaHC03, H2O, and brine and dried (MgS04). Filtration and concentration provided 13.56 g of product which was used without purification. 1 H-NMR (CDCI3) δ 10.6 (s, 1 H), 4.3 (s, 2H), 0.80 (s, 9H), 0.03 (s, 6H). TBD S- Part C. Preparation of N-butvl. N-benzvl-4-(t-butvldimethvlsilvloxv)-2- butyπamide In a flame-dried flask, 0.279 g NaH (80% dispersion in mineral oil) was washed with 5 mL pentane (3x) while maintaining a N2 atmosphere. The NaH was then suspended in 50 mL anhydrous benzene to which was added dropwise at room temperature a solution of 2.0 g 4-(t-butyldimethylsilyloxy)-2- butynoic acid in 45 mL benzene. After 45 minutes 4.05 mL (COCI)2 was added and the reaction stirred overnight. The mixture was filtered through glass fiber paper to remove NaCI and the clear filtrate concentrated. The residue was dissolved in 95 mL benzene and concentrated again. The crude residual acid chloride was used immediately as described below. To an ice-cold solution of 0.350 g butylbenzylamine and 0.447 mL diisopropylethylamine in 11 mL dry benzene under N2 was added a solution of the above acid chloride in 11 mL benzene. After stirring overnight with gradual warming to room temperature, the reaction was poured into H2O and extracted with Et2θ (3x). The combined organic extracts were washed with brine and dried (MgSθ4). Filtration and concentration provide crude product which was purified by flash chromatography with a 10%-15% Et2θ/hexanes gradient to give 0.39 g of product. 1 H-NMR (CDCI3) δ 7.30-7.15 (m, 5H), 4.7 and 4.55 (s, 2H), 4.4 and 4.38 (s, 2H), 3.40 and 3.22 (t, 2H), 1.6-1.4 (m, 2H), 1.30-1.18 (m, 2H), 0.90- 0.75 (m, 12H), 0.03 and 0.01 (s, 6H). [product is a mixture of rotamers] Part P. Preparation of N-butyl. N-benzyl-4-hvdroxy-2-butvnamide To an ice-cold solution of 0.61 g N-butyl, N-benzyl-4-(t- butyldimethylsilyl-oxy)-2-butynamide in 17 mL CH3CN under N2 was added dropwise 0.61 mL 48% HF. The reaction was stirred 2 hours at ice bath temperature, then neutralized by the careful addition of 10% NaHC03. The reaction was transferred to a separatory funnel, diluted with H2O and extracted with Et2θ. The combined organics were washed with 10% NaHC03, H2O, and brine and dried (MgS04). Filtration and concentration provided 0.27 g of product which was used as is. 1 H-NMR (CDCI3) δ 7.40-7.20 (m, 5H), 4.80 (s, 1 H), 4.60 (s, 1 H), 4.43- 4.37 (dd, 2H), 4.20-4.05 (bs, 1 H), 3.50-3.40 (t, 2H), 3.30-3.20 (t, 2H), 1.60- 1.40 (m, 2H), 1.40-1.20 (m, 2H), 0.95-0.80 (2t, 3H). [product is a mixture of rotamers] Part E. Preparation of N-butyl. N-benzyl-4-bromo-2-butvnamide To an ice-cold solution of 0.27 g N-butyl, N-benzyl-4-hydroxy-2- butynamide in 11 mL CH2CI2 in a N2 atmosphere was added 0.582 g CBr4. After stirring 10 min, 0.345 g Ph3P was added and the reaction stirred overnight with gradual warming to room temperature. The reaction was diluted with H2O and extracted with CH2CI2. The combined organics were washed with brine and dried (Na2Sθ4). Filtration, concentration, and flash chromatography using a 20%-40% Et2θ/hexanes gradient gave 0.26 g of product. 1 H-NMR (CDCI3) δ 7.40-7.20 (m, 5H), 4.75 and 4.60 (s, 2H), 4.21 and 4.00 (d, 1 H), 3.42 and 3.26 (t, 2H), 1.50 amd 1.30 (m, 2H), 0.98-0.83 (2t, 3H). [product is a mixture of rotamers] Part F. Preparation of N-butyl. N-benzyl-2-(aminocarbonvhethvnylmethyl 4- ethyl-2-propyl-1-[[2'-fN-triDhenvlmethyl(tetrazol-5-vn biphenyl-4- yl]methyl]imidazole-5-carboxylate To a solution/suspension of 0.55 g 4-ethyl-2-propyl-1 -[[2'-(N- triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylic acid, 0.26 g N-butyl, N-benzyl-4-bromo-2-butynamide, and 0.12 g powdered K2CO3 in 3 mL DMF was added in one portion 0.14 g Kl. The reaction was stirred 3 h at room temperature under N2, then partitioned between 8 mL H2O and 40 mL EtOAc. The organic extract was washed once with ice-cold 0.1 N Na2S2θ3, H2O, and brine, and dried (MgS04). Filtration, evaporation and flash chromatography using a 30%-50% EtOAc/hexanes gradient provided 0.65 g of product. 1 H-NMR (CDCI3) δ 7.87 (br d, 1 H), 7.50-7.40 (m, 2H), 7.38-7.16 (m, 15 H), 7.10-7.00 (m, 2H), 7.00-6.90 (m, 6H), 6.78-6.65 (m, 2H), 5.41 and 5.35 (s, 2H), 4.81 and 4.79 (s, 2H), 4.70 and 4.60 (s, 2H), 3.40 and 3.25 (t, 2H), 2.95 and 2.83 (q, 2H), 1.75-1.60 (m, 2H), 1.57-1.40 (m, 2H), 1.35-1.14 (m, 5H), 0.95-0.80 (2t, 6H). [product is a mixture of rotamers] Part G. Preparation of N-butyl. N-benzyl-2-(aminocarbonyl.ethvnylmethyl 4- ethyl-2-propyl-1 -[[2'-M H-tetrazol-5-vnbiphenyl-4-yl]methyl]imidazole-5- carboxylate To a solution of 0.55 g N-butyl, N-benzyl-3-carboxamido-2-propynyl 4- ethyl-2-propyl-1 -[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4- yl]methyl]imidazole-5-carboxylate in 14 mL MeOH at room temperature was added 5 drops of 6N HCI. After stirring overnight, the reaction was evaporated to dryness and the residue purified by flash chromatography using a 0%-5% MeOH/CHCl3 gradient to provide 0.36 g of product. MS (NH3-CI) 644.4 (M+H)+, 680.4 (M+NH4) + . lϋ Preparation of N. N-diphenyl-2-(aminocarbonvπethvnylmethyl 4-ethyl-2- proDyl-1- f2'-(1 H-tetrazol-5-vπbiDhenyl-4-vnmethvnimidazole-5-carboxylate TBDMS-0 0 S ≡≡≡— CO-OEt Part A. Preparation of Ethvl 4-(t-butyldimethvlsilvloxv)-2-butvnoate To a solution/suspension of 2.0 g of 4-(t-butyldimethylsilyloxy)-2- butynoic acid and 1.48 g Na2C03 in 37 mL DMF under N2 was added slowly 1.58 mL Et2Sθ4. After stirring overnight, the reaction was diluted with EtOAc and washed several times with H2O. The organic extract was then washed with brine and dried over MgSθ4. Filtration, evaporation and flash chromatography with a 5%-10% Et2θ/hexanes gradient provided 1.58 g of pure product. 1 H-NMR (CDCI3) δ 4.3 (s, 2H), 4.10 (q, 2H), 1.20 (t, 3H), 0.80 (s, 9H), 0.03 (s, 6H). Part B. Preparation of N. N-diphenyl-4-(t-butyldimethylsilyloxy)-2-butvnamide To a solution of 1.4 mL Mβ3AI (2.0M in hexanes) in 3.6 mL anhydrous CH2CI2 under N2 was added 0.49 g of diphenylamine in one portion. After stirring 30 min, 0.35 g ethyl 4-(t-butyldimethylsilyloxy)-2-butynoate in 0.4 mL CH2CI2 was added dropwise. The reaction was stirred overnight at room temperature, then heated in an oil bath at 35° overnight. The reaction was quenched by the addition of a few drops of 1 N HCI, diluted with H2O, and extracted with CH2CI2. The combined organics were with H2O and brine and dried over Na2S04. Filtration, evaporation, and flash chromatography with a 10-15% Et2θ/hexanes gradient provided 0.31 g of product. 1 H-NMR (CDCI3) δ 7.50-7.20 (m, 10H), 4.25 (s, 2H), 0.84 (s, 9H), 0.02 (s, 6H). Part C. Preparation of N. N-diphenyl-4-hvdroxy-2-butvnamide By employing the procedure described in Example 5, Part D, there was obtained from 0.91 g N, N-diphenyl-4-(t-butyldimethylsilyloxy)-2-butynamide 0.45 g of pure product. 1 H-NMR (CDCI3) δ 7.43-7.15 (m, 10H), 4.10 (s, 2H), 3.05 (br s, 1 H). Br ≡≡ — CO-N(Ph) 2 Part P. Preparation of N. N-diphenvl-4-bromo-2-butvnamide By employing the procedure described in Example 5, Part E, there was obtained from 0.45 g N, N-diphenyl-4-hydroxy-2-butynamide 0.54 g of product. H-NMR (CDCI3) δ 7.43-7.2 (m, 10H), 4.0 and 3.78 (s, 2H). [product is a mixture of rotamers] Part E. Preparation of N-butvl. N-benzvl-2-(aminocarbonvnethvnvlmethvl 4- ethvl-2-propvl-1 -[[2'-(N-triphenvlmethvl(tetrazol-5-vn)biphenvl-4- vl]methvl1imidazole-5-carboxvlate By employing the procedure described in Example 5, Part F, there was obtained from 0.56 g N, N-diphenyl-4-bromo-2-butynamide 1.16 g of pure product. 1 H-NMR (CDCI3) δ 7.90-7.85 (m, 1 H), 7.44-7.39 (m, 2H), 7.37-7.17 (m, 20H), 7.15-7.02 (m, 2H), 6.95-6.85 (m, 6H), 6.80-6.78 (m, 2H), 5.40 (s, 2H), 4.60 (s, 2H), 2.79 (q, 2H), 2.58 (t, 2H), 1.65 (m, 2H), 1.22 (t, 3H), 0.90 (t, 3H). Part F. Preparation of N-butvl. N-benzvl-2-(aminocarbonvnethvnylmethvl 4- ethvl-2-propvl-1-r[2'-(1 H-tetrazol-5-vnbiphenvl-4-vl]methvl]imidazole-5- carboxvlate By employing the procedure described in Example 5, Part G, there was obtained from 1.16 g N, N-diphenyl-3-carboxamido-2-propynyl 4-ethyl-2- propyl-1-[[2 , -(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5- carboxylate 0.60 g of pure product. 1 H-NMR (CDCI3) δ 7.83 7.80 (m, 1 H), 7.60-7.50 (m, 2H), 7.44-7.40 (m, 1 H), 7.40-7.20 (m, 8H), 7.20-7.06 (m, 4H), 6.82-6.78 (m, 2H), 5.40 (s, 2H), 4.61 (s, 2H), 2.63 (q, 2H), 2.42 (t, 2H), 1.75-1.60 (m, 2H), 1.05 (t, 3H), 0.91 (t, 3H). Preparation of N-phenyl-2-(aminocarbonvπethyl 4-ethyl-2-propyl-1-[f2'-(1 H- tetrazol-5-vπbiphenyl-4-yl]methyl1imidazole-5-carboxylate Part A. Preparation of N-phenyl-2-(aminocarbonvπethyl 4-ethyl-2-propyl-1 - [[2'- N-triphenylmethyl(tetrazol-5-vn biphenyl-4-yl methyl]imidazole-5- carboxylate To a solution/suspension of 0.66 g 4-ethyl-2-propyl-1 -[[2'-(N- triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylic acid, 0.23 g 2-bromo-N-phenylpropionamide, and 0.15 g K2CO3 in 7mL of DMF was added 0.17 g of Kl. The reaction was stirred 10 minutes at room temperature, then heated in a N2 atmosphere at 70°C overnight. The reaction was partitioned between H2O and EtOAc, and the organic extract washed with brine and dried with MgS04. Filtration, concentration, and flash chromatography with a 10-60% EtOAc/hexanes gradient provided 0.35 g of pure product. 1 H-NMR (CDCI3) δ 8.70 and 7.98 (br s, 1 H), 7.85 (m, 1 H), 7.50-7.40 (m, 4H), 7.37-7.20 (m, 13H), 7.11-7.00 (m, 3H), 6.99-6.91 (m, 5H), 6.80-6.77 (m, 2H), 5.40 (s, 2H), 5.35 and 4.28 (q, 1 H), 2.99 (q, 2H), 2.55 (t, 2H), 1.78- 1.60 (m, 2H), 1.53 and 1.48 (d, 3H), 1.37 (t, 3H), 0.87 (t, 3H). Part B. Preparation of N-phenyl-2-(aminocarbonyπethyl 4-ethyl-2-propyl-1 - [[2'-(1 H-tetrazol-5-vπbiphenyl-4-yl methyl]imidazole-5-carboxylate A solution of 0.05 g N-phenyl-2-(aminocarbonyl)ethyl 4-ethyl-2-propyl- 1-[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5- carboxylate in 2.5 mL MeOH was refluxed overnight under N2. The reaction was evaporated to dryness and the residue immediately purified by flash chromatography with 0-5% MeOH/CHCl3 gradient to give 0.0226 g of pure product. 1 H-NMR (CDCI3) δ 8.10 (br s, 1 H), 7.88 (m, 1 H), 7.60-7.45 (m, 2H), 7.40-7.23 (m, 3H), 7.20-7.10 (m, 2H), 7.09-6.96 (m, 3H), 6.81-6.75 (m, 2H), 5.40 (s, 2H), 5.27 (q, 1 H), 2.72 (q, 2H), 2.40 (t, 2H), 1.68-1.60 (m, 2H), 1.52 (d, 3H), 1.08 (t, 3H), 0.88 (t, 3H). Preparation of N-butyl. N-benzyl-4-(aminocarbonv0propyl 4-ethyl-2-propyl-1- [[2'-(1 H-tetrazol-5-vπbiphenyl-4-yl]methyl1imidazole-5-carboxylate Part A. Preparation of N-butvl. N-benzvl-4-hvdroxv-butanamide To a solution of 23 mL of Me3AI (2.0M in hexanes) in 24 mL of CH2CI2 was added in a N2 atmosphere 8.33 mL butylbenzylamine. The mixture was stirred 30 minutes at room temperature before adding 0.89 mL of g- butyrolactone. The reaction was stirred overnight at room temperature, then quenched with 1 N HCI to pH 2-3, and extracted with CH2CI2. The combined organics were washed with H2O and brine, and dried over Na2S04. Filtration, evaporation, and flash chromatography with a 0-5% MeOH/CHCl3 gradient provided 2.07 g of product. 1 H-NMR (CDCI3) δ 7.40-7.17 (m, 5H), 4.61 and 4.59 (s, 2H), 3.75 and 3.65 (t, 2H), 3.38 and 3.21 (t, 2H), 2.58 and 2.47 (t, 2H), 2.00-1.80 (m, 2H), 1.60-1.43 (m, 2H), 1.38-1.22 ( m, 2H), 0.97-0.85 (2t, 3H). Part B. Preparation of N-butvl. N-benzvl-4-(aminocarbonynpropvl 4-ethvl-2- propyl-1-fr2'-(tetrazol-5-vhbiphenvl-4-vl1methvllimidazole-5-carboxvlate To a solution of 0.40 g 4-ethyl-2-propyl-1-[[2'-(1 H-tetrazol-5-yl)biphenyl- 4-yl]methyl]imidazole-5-carboxylic acid in 50 mL anhydrous THF was added 0.27 g CDI in one portion. After stirring overnight at room temperature under N2, there was added a solution of the sodium alkoxide of N-butyl, N-benzyl-4- hydroxy-butanamide (prepared from 0.48 g of the alcohol with NaH) in 5 mL THF. After 24 hours at room temperature, the reaction was poured into cold brine and extracted with CH2Cl2/i-PrOH (4:1 ). The organic extract was dried (MgSθ4), filtered, evaporated, and purified by flash chromatography using 0- 15% MeOH/CH2Cl2 to give 0.16 g of product. 1 H-NMR (CDCI3) δ 13.5 (br s, 1 H), 7.8 (m, 1 H), 7.51-7.4 (m, 3H), 7.38- 7.10 (m, 4H), 7.10-7.08 (m, 1 H), 7.08-7.00 (m, 2H), 6.82-6.77 (m, 2H), 5.41 and 5.39 (s, 2H), 4.60 and 4.49 (s, 2H), 4.25 and 4.15 (t, 2H), 3.37 and 3.18 (t, 2H), 2.85-2.68 (m, 2H), 2.55-2.45 (m, 2H), 2.40 (t, 2H), 2.01 -1.90 (2t, 2H), 1.65-1.40 (m, 2H), 1.28-1.20 (m, 4H), 0.92-0.80 (2t, 6H). Preparation of Preparation of N. N-dipentvl-4-(aminocarbonvnpropvl 4-ethvl-2- propyl-1-f[2'-(tetrazol-5-ynbiphenvl-4-vl1methvl1imidazole-5-carboxvlate Part A. Preparation of N. N-dipentvl-4-hvdroxv-butanamide By employing the method described in Example 8, Part A, there was obtained from 0.89 mL g-butyrolactone and 9.41 mL dipentylamine 2.51 g of pure product. 1 H-NMR (CDCI3) δ 3.99 (br s, 1 H), 3.65 (t, 2H), 3.37-3.20 (m, 4H), 2.43 (t, 2H), 1.95-1.83 (m, 2H), 1.62-1.43 (m, 4H), 1.40-1.20 (m, 8H), 0.97- 0.80 (2t, 6H). Part B. Preparation of N. N-diDentvl-4-aminocarbonvlpropvl 4-ethvl-2-propvl- 1-fr2'-(1 H-tetrazol-5-vnbiphenvl-4-vl]methvl]imidazole-5-carboxvlate By employing the method described in Example 8, Part B, there was obtained from 0.47 g N, N-dipentyl-4-hydroxy-butanamide, 0.40 g 4-ethyl-2- propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylic acid, and 0.27 g CDI 0.12 g of pure product. 1 H-NMR (CDCI3) δ 13.3 (br s, 1 H), 7.81 (m, 1 H), 7.55-7.38 (m, 3H), 7.10-7.00 (m, 2H), 6.82-6.80 (m, 2H), 5.40 (s, 2H), 4.22 (t, 2H), 3.25 (t, 2H), 3.19 (t, 2H), 2.84 (m, 2H), 2.50 (t, 2H), 2.40 (t, 2H), 2.01 (m, 2H), 1.70-1.40 (m, 6H), 1.37-1.18 (m, 11 H), 0.95-0.80 (m, 9H). Preparation of 2-(N-Benzovlpiperidin-2-yltethvt 1 -f(2'-(n- butoxycarbonvlaminosulfonvn-3-fluorobiphenvnmethvl]-4-ethvl-2- propylimidazolecarboxvlate. Part A. Preparation of N-benzovl-2-DiDeridineethanol To a solution of benzoic anhydride (16.6 g, 73.5 mmol) and triethylamine (8.2 g, 81.1 mmol) in 150 mL of methylene chloride, was added 2-piperidine-ethanol (10.0 g, 77.5 mmol). A slight exotherm was observed and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was washed in turn with 200 mL of 1N hydrochloric acid, 200 mL of saturated sodium bicarbonate, and 100 mL brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give 14.0 g of a crude product. This was purified by flash chromatography (silica gel, 100% ethyl acetate) to yield 9.47 g (55%) of product as a light amber oil. MS: m/e 234, [M+H]+; 1 H NMR (300 MHz, CDCI3): δ 1.50-1.75 (br m, 6H); 1.84-2.03 (br m, 1 H); 2.06 (complex t, 1 H); 2.91 (br t, J=13 Hz, 1 H); 3.47 (t, J=11.7 Hz, 1 H); 3.60-3.71 (br m, 2H); 4.15 (br s, 2H); 4.96 (br d, J=12 Hz, 1 H); 7.41 (br s, 5H). Part B. Preparation of 1-.2-fluoro-4-iodobenzvn-4-ethyl-2-propyl-1 H- imidazole-5-carboxvlic acid. A solution of 30% hydrogen peroxide (5.2 mL, 50.9 mmol) in 80 mL of tetrahydrofuran was chilled in an ice bath . To this was added a solution of sodium dihydrogen phosphate monohydrate (5.2 g, 37.7 mmol) in 50 mL of water followed by a solution of 1 -(2-fluoro-4-iodobenzyl)-4-ethyl-2-propyl-1 H- imidazole-5-carboxaldehyde (10 g, 25 mmol) in 80 mL of tetrahydrofuran. To this reaction mixture, was slowly added over a 30 minute period, a solution of 80% sodium chlorite (5.65 g, 50 mmol) in 130 mL of water, maintaining the reaction temperature between +5° and +10°C. The yellow reaction mixture was then stirred at room temperature overnight. By the next day, the reaction mixture had become a turbid white solution, to which was added solid sodium sulfite (6.25 g, 49.6 mmol) followed by a solution of sodium sulfite (23.4 g, 186 mmol) in 100 mL of water. The reaction mixture was stirred for 30 minutes and its pH was adjusted to pH 12 with 3 sodium hydroxide, dissolving any precipitated solids. The tetrahydrofuran was stripped under vacuum and the aqueous residue was extracted with 250 mL of methylene chloride. The aqueous phase was stripped of any residual methylene chloride under vacuum and filtered through celite. The filtrate was chilled in ice and the product precipitated with the addition of 6 hydrochloric acid. The product was filtered, washed with ice cold water, and dried overnight, yielding 6.88 g (66%) of product as a white solid. MS: m/e 417 [M+H]+; 1 H NMR (300 MHz, DMSO-d6): δ 0.87 (t, J= 7.3 Hz, 3H); 1.16 (t, J=7.3 Hz, 3H); 1.63 (m, 2H): 2.61 (t, J=7.7 Hz, 2H); 2.81 (q, J=7.3 Hz, 2H); 5.52 (s, 2H); 6.33 (t, J=8.1 Hz,1 H); 7.51 (d, J=8.1 Hz, 1 H); 7.69 (d, J=9.5 Hz, 1 H). Part C. Preparation of 2-(N-Benzovlpiperidin-2-vnethvl 1-[2-fluoro-4- iodophenvnmethvl]-4-ethvl-2-propvlimidazolecarboxvlate. Oxalyl chloride (15 mL, 21.8 g, 172 mmol) was cautiously added to a flask containing the product from part B (1.5 g, 3.6, mmol), chilled in a ice bath. The cooling bath was removed and the reaction mixture was heated to reflux under nitrogen for 30 minutes. The excess oxalyl chloride was stripped under vacuum and the solid residue was dissolved in 15 mL dry methylene chloride. To the resulting solution was added a solution containing N- benzoyl-2-piperidineethanol (1.3 g, 5.5 mmol) and pyridine (1 mL, 0.98 g, 12 mmol) in 5 mL dry methylene chloride. The reaction was refluxed under nitrogen for two hours and then stirred at room temperature overnight. The reaction mixture was washed twice with 40 mL of 1 fjJ hydrochloric acid, then four times with 25 mL saturated sodium bicarbonate, and finally with 25 mL of brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give 2.56 g of crude product. This was purified by flash chromatography (silica gel, gradient: 50% hexane / 50% ethyl acetyate - 25%hexane / 75% ethyl acetate) to yield 1.77 g (78%) of product as a glass. MS: m/e 632, [M+H]+. Part D. Preparation of 2-fN-Benzoylpiperidin-2-ynethyl 1-[(2'-(t- butylaminosulfonyl -3-fluorobiphenvπmethyl]-4-ethyl-2- propylimidazolecarboxylate. _ A mixture of the product from part C (1.0 g, 1.6 mmol), 2-(t- butylamino)sulfonyl-phenyl boronic acid (0.55 g, 2.1 mmol), tetrabutylammonium bromide (0.05 g, 0.16 mmol), and potassium carbonate (0.60 g, 4.3 mmol) was suspended in 6 mL of toluene and 2 mL of water. The reaction mixture was degassed by evacuating and refilling with nitrogen. Tetrakistriphenylphosphine palladium(O) (0.1 g, 0.087 mmol) was added and the degassing procedure repeated. The reaction mixture was refluxed with efficient stirring overnight. The reaction mixture was poured into a separatory funnel containing 25 mL of ethyl acetate and the aqueous layer drained and discarded. The organic phase was washed in turn with 25 mL of water, two 25 mL portions of saturated sodium bicarbonate, and 25 mL of brine. The organic phase was then dried over anhydrous magnesium sulfate, filtered and stripped under vacuum to give 1.32 g of crude product. This was purified by flash chromatography (silica gel, gradient: 10% acetone / 30% ethyl acetate / 60% hexane - 20%acetone / 30% ethyl acetate / 50% hexane) to yield 0.82 g (72%) of product as a glass. MS: m/e 703, [M+H]+. Part E. Preparation of 2-(N-Benzoylpiperidin-2-v0ethyl 1-f(2'-(aminosulfonvπ- 3-fluorobiphenvπmethvn-4-ethyl-2-propylimidazolecarboxylate. A solution of the product from part D (0.82 g, 1.1 mmol) in 35 mL of trifluoroacetic acid was refluxed protected from moisture for 3 h. The trifluoroacetic acid was stripped under vacuum and the residue dissolved in 50 mL of methylene chloride. This solution was washed with two portions of 50 mL of saturated sodium bicarbonate and then with brine. The organic phase was dried over anhydrous magnesium sulfate, filtered, and stripped under vacuum to give 0.74 g (98%) of crude product as a glass. MS: m/e 661 , [M+H]+. This product was sufficiently pure to use in the next reaction. Part F. Preparation of 2-fN-Beπ2oylpiperidin-2-vttethvl 1-[(2'-(n- butoxvcarbonvlaminosulfonvn-3-fluorobiDhenvnmethvl]-4-ethvl-2- propvlimidazolecarboxvlate. To a solution containing the product from part E (0.74 g, 1.1 mmol) and 4-dimethylaminopyridine (0.63 g, 5.1 mmol) in a mixture of 5 mL of pyridine and 50 mL of methylene chloride, was added n-butyl chloroformate (0.65 g, 4.74 mmol) under a nitrogen atmosphere. The reaction mixture was stirred overnight at room temperature, and then washed in turn with four 100 mL portions of 1£J hydrochloric acid, 100 mL of saturated sodium bicarbonate, and 100 mL of brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and stripped under vacuum to give 0.88 g of crude product. This was purified by flash chromatography (silica gel, 0.5% acetic acid, 20% acetone, 30% ethyl acetate, 50% hexane) to give 0.61 g (72%) of product as a white solid foam. MS: m/e 761 , [M+H] + . Preparation of 4-ff5-((2-benzovnphenvlcarbonvloxvmethvn-4-chloro-2-n- propvlimidazol-1-vnmethvπ-3-fluoro-2'- isoamvloxvcarbonylaminosulfonvlbiphenvl. sodium salt. Part A. Preparation of 1 -[2'-(t-butylaminosulfonvπ-3-fluorobiphenyl-4- yl]methyl-4-chloro-2-n-propylimidazole-5-carboxaldehyde. 4-Chloro-2-n-propyl-imidazole-5-carboxaldehyde was prepared as described in U.S. Patent 4,760,083. The imidazole can then be converted to the title compound by using the methods of Example 1 , Parts A, B, and C. NMR (CDCI3) δ 9.77 (S,1 H), 8.16 (d, 1 H), 7.50 (m, 2H), 7.30 (m, 3H), 6.86 (t, 1 H), 5.63 (s, 2H), 3.55 (s, 1 H), 2.65 (m, 2H), 1.79 (m, 2H), 1.00 (m, 12H). Part B. Preparation of 2'-f N-t-butvhsulfonamido-4'ff4-chloro-5-hydroxymethyl- 2-n-propylimidazol-1 -vnmethyl]-3-fluorobiphenyl. 1 -[2'-(t-Butylaminosulfonyl)-3-fluorobiphenyl-4-yl]methyl-4-chloro-2-n- propylimidazole-5-carboxaldehyde (3.49 g, 7.10 mmol) was dissolved in methanol (30 mL). Sodium borohydride (0.32 g, 8.5 mmol) was added over 5 minutes. The reaction was complete within minutes. The reaction was poured into water and extracted with ethyl acetate (3X). The solvent was dried (MgSθ4) and the solvent removed in vacuo to yield 3.20 g of a tan powder. NMR (CDCI3) δ 8.18 (d, 1 H), 7.55 (m, 2H), 7.30 (m, 3H), 6.78 (t, 1 H), 5.49 (s, 2H), 4.56 (d, 2H), 3.76 (s, 1 H), 2..59 (m, 2H), 1.75 (m, 2H), 1.02 (s, 9H), 0.98 (t, 3H). Part C. Preparation of 4-[(5-((2-benzovπphenylcarbonyloxy)methyl-4-chloro- 2-n-propylimidazol-1 -yhmethyl]-2'-(N-t-butvπsulfonamido-3-fluorobiphenyl. 2-Benzoylbenzoic acid (0.23 g, 1.0 mmol), dicyclohexylcarbodiimide (0.21 g, 1.0 mmol), dimethylaminopyridine (0.01 g, 0.1 mmol), and 2'-(N-t- butyl)sulfonamido-4-[(4-chloro-5-hydroxymethyl-2-n-propylimidazol-1- yl)methyl]-3-fluorobiphenyl (0.50 g, 1.0 mmol) were all added to CH2CI2 (25 mL). The reaction was stirred at room temperature for 72 h. The reaction was filtered. The filtrate was washed with water, 10% citric acid, water, dried (MgSθ4) and the solvent removed in vacuo Xo yield 0.72 g. NMR (CDCI3) δ 8.16 (d, 1 H), 8.02 (d, 1 H), 7.6-7.3 (m, 11 H), 7.15 (t, 2H), 6.63 (t, 1 H), 5.04 (s, 2H), 4.93 (s, 2H), 3.67 (s, 1 H), 2.55 (m, 2H), 1.70 (m, 2H), 1.00 (m, 12H). Part D. Preparation of 4-[(5-((2-benzovnphenvlcarbonvloxv)methvl-4-chloro- 2-n-propvlimidazol-1-vl)methvl]-3-fluoro-2'-sulfonamidobiphenvl. 4[(5-((2-Benzoyl)phenylcarbonyloxy)methyl-4-chloro-2-n-propylimidazol- 1-yl)methyl]-2'-(N-t-butyl)sulfonamido-3-fluorobiphenyl (0.72 g, 1.0 mmol) was dissolved in trifluoroacetic acid (20 mL). The reaction was heated to reflux for 2 hours. It then was stirred at room temperature overnight. The solvent was removed in vacuo. The residue was taken up in CH2CI2. 10% Sodium bicarbonate was added until the aqueous was neutral. The CH2CI2 layer was separated, dried, and the solvent removed in vacuo. Column chromatography using 50% ethyl acetate in hexane yielded 0.48 g. NMR (CDCI3) δ 8.15 (d, 1 H), 8.03 (d, 1 H), 7.7-7.1 (m, 13H), 6.67 (t, 1 H), 5.03 (s, 2H), 4.91 (s, 2H), 4.48 (s, 2H), 2.55 (m, 2H), 1.75 (m, 2H), 0.98 (t, 3H). Part E. Preparation of 4-f(5-((2-benzovnphenvlcarbonvloxv methvl-4-chloro- 2-n-propvlimidazol-1-vhmethvn-3-fluoro-2'- isoamvloxvcarbonvlaminosulfonvlbiphenvl. sodium salt. 4-[(5-(2-Benzoyl)phenylcarbonyloxy)methyl-4-chloro-2-n-propylimidazol- 1-yl)methyl]-3-fluoro-2'-sulfonamidobiphenyl (0.24 g, 0.37 mmol) and dimethylaminopyridine (0.28 g, 2.3 mmol) were added to a mixture of CH2CI2 (25 mL) and pyridine (1 mL). i-Amylchloroformate solution (2.25 M in toluene, 1.0 mL, 2.3 mmol) was added to the reaction and it was stirred at room temperature for 48 h. The reaction was diluted with additional CH2CI2 and washed with 10% citric acid solution (3X). The solution was dried (MgS04) and the solvent removed in vacuo. The material was then washed with hexane to yield 0.22 g of a solid. The product was titrated with 0.09 M KOH and the water was removed in vacuo. NMR (CDCI3) δ 8.03 (m, 2H), 7.7-7.0 (m, 13H), 6.65 (m, 1 H), 4.91 (s, 2H), 4.79 (s, 2H), 3.49 (m, 2H), 2.57 (m, 2H), 1.75 (m, 2H), 0.98 (t, 3H), 0.64 (d, 6H). Example 12 Preparation of 1 -((2'-((n-butyloxycarbonylamino)sulfonyl)-3-fluoro-M .1 '- biphenvπ-4-vnmethvπ-2-fn-propyl)-4-ethyl-5-f2-(phenoxy)phenoxy)acetyl-1 H- imidazole Part A. Preparation of 1-(4-bromo-2-fluorobenzyl)-2-(n-propyl)-4-ethyl-5-(1 - (trimethylsilyloxy)ethenyl)-1 H-imidazole To a solution of 2.50 g (6.81 mmol) of 1-(4-bromo-2-fluorobenzyl)-2-(n- propyl)-4-ethyl-5-acetyl-1 H-imidazole (6J7 R1 = 2-F, R 2 = 4-Br, n = 0; prepared using the procedures of Example 3, Parts A and B) in 80 mL anhydrous THF was added 7.59 mL trimethylsilyl triflate (40.8 mmol) under nitrogen at 22°C, followed by 11.38 mL (81.9 mmol) triethylamine. The mixture was stirred at 22°C for 2.5 hours.and then diluted with 100 mL of anhydrous ethyl ether and quenched with 10 mL of saturated NaHC03 solution. The organic layer was washed with saturated NaHCθ3 solution, dried over Na2Sθ4, and filtered. Solvents were then removed under reduced pressure yield 2.69 g (90%) of the title compound as a brown oil, which was used without further purification. 1 H NMR (300 MHz, CDCI3): δ 0.14 (s, 9H); 0.84 (t, 3H); 1.16 (t, 3H); 1.68 (m, 2H); 2.41 (t, 2H); 2.56 (q, 2H); 4.30 (s, 1 H); 4.43 (s, 1 H); 5.03 (s, 2H); 6.44 (t, 1 H); 7.10 (m, 2H). Part B. Preparation of 1 -(4-bromo-2-fluorobenzyl)-2-(n-propyl)-4-ethyl-5- bromoacetyl-1 H-imidazole To 2.69 g (6.13 mmol) of 1-(4-bromo-2-fluorobenzyl)-2-(n-propyl)-4- ethyl-5-(1-(trimethylsilyloxy)ethenyl)-1 H-imidazole in 100 mL THF at 0°C was added 1.09 g (6.13 mmol) of NBS. After stirring for 30 min, the solution was poured into saturated NaHC03 solution. The mixture was extracted with anhydrous ethyl ether, dried over Na2Sθ4 and filtered. The filtrate was evaporated under reduced pressure to give 2.32 g (85%) of the title compound as a brown oil, which was used without further purification. 1 H NMR (300 MHz, CDCI3): δ 0.96 (t, 3H); 1.42 (t, 3H); 1.76 (m, 2H); 2.46 (t, 2H); 3.02 (q, 2H); 5.30 (s, 2H); 5.50 (s, 2H); 6.59 (t, 1H); 7.14 (m, 2H). Part C. Preparation of 2-phenoxyphenol A solution of 23.4 g (74.9 mmol) of boron tribromide-dimethyl sulfide complex in 150 mL of 1 ,2-dichloroethane was added dropwise to 3.00 g (15.0 mmol) of 2-methoxyphenyl phenyl ether in 50 mL dichloroethane at room temperature. The mixture was stirred at reflux overnight. 50 mL 3M NaOH was added to quench the reaction. After separation of layers, the organic layer was extracted with 3 x 100 mL 3M NaOH. The combined aqueous layer was acidified with cone. HCI, and the precipitated product was extracted with 3 x 150 mL ethyl ether. After washing with brine solution, drying over MgSθ4, and filtering, solvents were evaporated under reduced pressure to give 2.30 g (82.4%) of an off-white solid, which was used without further purification. 1 H NMR (300 MHz, CDCI3): δ 5.57 (s, 1 H); 6.81-6.90 (m, 2H); 7.01-7.07 (m, 4H); 7.12 (t, 1 H, J = 7.3 Hz); 7.31 -7.38 (m, 2H). Part D. Preparation of 1-(4-bromo-2-fluorobenzyl)-2-(n-propyl)-4-ethyl-5-(2- (phenoxy)phenoxy)acetyl-1 H-imidazole To a solution of 0.63 g (3.36 mmol) of 2-phenoxyphenol and 0.62 g (4.48 mmol) of K2CO3 in 75 mL acetone at ambient temperature was added 1.00 g (2.24 mmol) of 1 -(4-bromo-2-fluorobenzyl)-2-(n-propyl)-4-ethyl-5- bromoacetyl-1 H-imidazole obtained from Part B of Example 11 in 25 mL acetone. After stirring at reflux overnight, the reaction mixture was poured into water and extracted with 3 x 100 mL ethyl acetate. The combined organic layers were washed with brine, dried over MgSθ4, filtered, and the solvents evaporated under reduced pressure. The crude product was purified by flash column chromatography using 10-40% ethyl acetate in hexane, which provided 0.16 g (6.3%) of a clear oil after evaporation of solvents under reduced pressure. 1 H NMR (300 MHz, CDCI3): δ 0.95 (t, 3H, J = 7.3 Hz); 1.29 (t, 3H, J = 7.3 Hz); 1.66 (m, 2H); 2.60 (m, 2H); 2.81 (q, 2H, J = 7.3 Hz); 5.00 (s, 2H); 6.38 (t, 1 H, J = 7.8 Hz); 6.89-7.29 (m, 10H). Part E. Preparation of 1-((2'-(t-butylaminosulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-2-(n-propyl)-4-ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H-imidazole From 0.16 g (0.29 mmol) of 1 -(4-bromo-2-fluorobenzyl)-2-(n-propyl)-4- ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H-imidazole, using 0.12 g (0.47 mmol) of 2-(t-butylamino)sulfonylphenyl boronic acid, 0.12 g (0.86 mmol)potassium carbonate, 0.016 g (0.05 mmol) tetrabutylammonium bromide, 0.02 g (0.02 mmol) tetrakis(triphenylphosphine)palladium(0), with 1 mL of water and 2 mL of toluene as solvent, 0.08 g (40%) of the title compound was obtained following the procedure of Example 3, Part F, after purification by preparative TLC (silica gel; 20% acetone, 30% ethyl acetate, 50% hexane). 1 H NMR (300 MHz, CDCI3): δ 0.97 (m, 12H, overlapping t-butyl singlet and methyl triplet); 1.32 (t, 3H, J = 7.3 Hz); 1.72 (m, 2H); 2.63 (t, 2H, J = 7.3 Hz); 2.83 (q, 2H, J = 7.3 Hz); 3.57 (s, 1 H); 5.06 (s, 2H); 5.58 (s,2H); 6.61 (t, 1 H, J = 8.1 Hz); 6.87-7.09 (m, 7H); 7.12 (d, 1 H, J = 8.1 Hz); 7.23-7.29 (m,5H); 7.51 (m, 2H); 8.15 (d, 1 H, J = 7.7 Hz). Part F. Preparation of 1-((2'-(aminosulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-2-(n-propyl)-4-ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H-imidazole From 0.08 g (0.12 mmol) of 1-((2'-(t-butylaminosulfonyl)-3-fluoro-(1 ,1'- biphenyl)-4-yl)methyl)-2-(n-propyl)-4-ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H- imidazole in 6 mL of trifluoroacetic acid, 0.08 g (100%) of the title compound was obtained, following the precedure of Example 3, Part G, with a 5 hr reflux period. MS m/e = 628, [M=H]+; 1 H NMR (300 MHz, CDCI3): δ 0.98 (t, 3H, J = 7.3 Hz); 1.33 (t, 3H, J = 7.3 Hz); 2.66 (t, 2H, J = 7.3 Hz); 2.83 (q, 2H, J = 7.3 Hz); 4.20 (br s, 2H); 5.04 (s, 2H); 5.56 (s,2H); 6.63 (t, 1 H, J = 7.8 Hz); 6.84- 7.09 (m, 9H); 7.18 -7.29 (m,4H); 7.48-7.61 (m, 2H); 8.14 (d, 1 H, J = 7.8 Hz). Part G. Preparation of 1-((2'-((n-butyloxycarbonylamino)sulfonyl)-3-fluoro- (1 ,1 '-biphenyl)-4-yl)methyl)-2-(n-propyl)-4-ethyl-5-(2- (phenoxy)phenoxy)acetyl-1 H-imidazole From 0.08 g (0.13 mmol) of 1 -((2'-(aminosulfonyl)-3-fluoro-(1 ,1 '- biphenyl)-4-yl)methyl)-2-(n-propyl)-4-ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H- imidazole and using 0.10 g (0.82 mmol) of 4-N,N-dimethylaminopyridine, 100 mL, 0.11g (0.73 mmol) of n-butyl chloroformate, with 1 mL pyridine and 10 mL methylene chloride as solvent, 0.05 g (54%) of title was obtained following the procedure of Example 3, Part H, with a 16 hr reaction time and after purification by prep TLC (silica gel; 20% acetone, 30% ethyl acetate, 50% hexane). MS m/e = 728, [M=H]+; 1 H NMR (300 MHz, CDCI3): δ 0.83 (t, 3H, J = 7.3 Hz); 0.98 (t, 3H, J = 7.3 Hz); 1.18 (m,2H); 1.32 (t, 3H, J = 7.3 Hz); 1.43 (m,2H); 1.73 (m,2H) 2.67 (t, 2H, J = 7.7 Hz); 2.82 (q, 2H, J = 7.3 Hz); 3.98 (t, 2H, J = 6.6 Hz); 5.05 (s, 2H); 5.57 (s,2H); 6.59 (t, 1 H, J = 7.7 Hz); 6.86-7.10 (m, 6H); 7.16 -7.33 (m,6H); 7.54-7.66 (m, 2H); 8.25(d, 1 H, J = 7.7 Hz). Compounds 13-488 in tables 1 -5 can be prepared by the prodedures described in examples 1 -12 employing the appropriately substituted starting materials. Table 1. Ex R6 R8 Ra R13 R2 m.p. n-propyl ethyl CH 3 (CH2)2θ2C-NHS0 2 - 2-F n-propyl ethyl (CH3)2CHCH2θ 2 C-NHSθ2- 2-F n-propyl ethyl CH3(CH2)3θ2C-NHS0 - 2-F n-propyl ethyl CH3(CH 2 )3θ 2 C-NHSθ2- 2-CI CH 3 (CH )3θ2C-NHS0 2 - 2-F h CH3(CH2)3θ2C-NHSθ2- 2-CI n-propyl ethyl n-propyl ethyl n-propyl ethyl n-propyl ethyl CH3(CH2)2θ2C-NHSθ2- 2-F n-propyl ethyl (CH3) 2 CH(CH2)2θ2C-NHS0 2 - 2-F n-propyl ethyl CH3(CH2)2θ2C-NHSθ2- 2-F m n-propyl ethyl (CH3)2CH(CH 2 )2θ2C-NHS0 2 - 2-F n-propyl ethyl CH 3 (CH2)2θ2C-NHSθ2- 2-F n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F n-propyl ethyl CH 3 (CH 2 )2θ 2 C-NHSθ2- 2-F n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F n-propyl ethyl V O (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 34 n-propyl ethyl 2-F u 35 n-propyl CI 2-F 36 n-propyl ethyl 2-F 37 n-propyl ethyl (M+H)+=719.2 o 38 n-propyl ethyl -i δo (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F 39 n-propyl ethyl 40 n-propyl ethyl 41 n-propyl ethyl 42 n-propyl ethyl n-propyl ethyl (CH3)(CH2)2θ2C- HS0 2 - H n-propyl ethyl (CH3)2CHθ2C-NHSθ2- H n-propyl ethyl P CH2θ2C-NHSθ2- H n-propyl ethyl (CH3(CH2)3-NH-CO-NHS02- 2-F n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F n-propyl ethyl (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F n-propyl ethyl (CH 3 )(CH2)3θ2C-NHS0 2 - 2-F n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - 2-F n-propyl ethyl (CH3)2CHθ2C- HSθ2- 2-F n-propyl ethyl 2-F n-propyl ethyl 2-F 71 n-propyl ethyl -CN H H 72 n-propyl ethyl -CN 4 H H 73 n-propyl ethyl 74 n-propyl ethyl -CN 4 H H 75 n-propyl ethyl 76 n-propyl ethyl 77 n-propyl ethyl 78 n-propyl ethyl 79 n-propyl ethyl -CN 4 H 2-F dd 80 n-propyl ethyl PhCH2θ 2 C-NHS0 2 - 2-F 81 n-propyl ethyl Ph(CH )2θ C-NHSθ2- 2-F 82 n-propyl ethyl Ph(CH )3θ 2 C-NHSθ2- 2-F 83 n-propyl ethyl Ph(CH 2 ) 4 θ2C-NHSθ2- 2-F 84 n-propyl ethyl (CH3(CH2)3-NH-CO-NHS02- 2-F 85 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHSC>2- 2-F 86 n-propyl ethyl (CH3)2CH(CH2)θ2C-NHS0 - 2-F 87 n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - 2-F 88 n-propyl ethyl (CH 3 )2CH(CH2)2θ2C-NHS0 2 - 3-F (M+H)+=754 89 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHS0 2 - 2-CH 3 0- 90 n-propyl ethyl Ph(CH 2 )2θ 2 C-NHSθ2- 2-CH 3 91 n-propyl ethyl (CH 3 )2CH(CH2)2θ 2 C-NHSθ2- 3-CH 3 0- 92 n-propyl ethyl (CH3) 2 CH(CH2)2θ2C-NHS0 2 - 2-N0 2 - 93 n-propyl ethyl (CH3(CH2)3-NH-CO-NHS0 - 2-CN 94 n-propyl ethyl (CH3) 2 CH(CH2)2θ2C-NHS0 - 3-CH 3 S- 95 n-propyl ethyl (CH3)2CH(CH2)θ2C-NHS0 2 - 3-CH3SO2- 96 n-propyl ethyl (CH3)(CH2)3θ2C-NHSθ2- 3-CH3SO- 97 n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - 2-Br 98 n-propyl ethyl (CH3)2CHθ2C- HSθ2- 3-I 99 n-propyl ethyl PhCH2θ2C-NHSθ2- 2-F ■ CH j NH-CO- H-SO j -Ph 100 n-propyl ethyl -f Ph(CH 2 )2θ2C-NHSθ2- H 101 n-propyl ethyl Ph(CH 2 )3θ2C-NHSθ2- 3-F 102 n-propyl ethyl Ph(CH2) 4 0 2 C-NHS0 2 - 3-F •CH, CO-NH-SO,-NH-Ph 103 n-propyl ethyl _^ (CH3(CH2)3-NH-CO-NHS0 2 - 2-F 104 n-propyl ethyl 2 ' -(CH3)2CH(CH 2 )2θ2C-NHSθ2- 2-CI 105 n-propyl ethyl 2'-(CH3)2CH(CH2)2θ2C-NHS0 2 - 2-CI 106 n-propyl ethyl 2"-(CH3)2CH(CH2)2θ2C-NHSθ2- 2-CI 107 n-propyl ethyl 2'-(CH3)2CH(CH2)2θ2C-NHS0 - 2-CI 108 n-propyl ethyl 2 , -(CH 3 ) 2 CH(CH2)2θ2C-NHS0 2 - 2-CI 109 n-propyl ethyl 2 , -(CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-CI 110 n-propyl ethyl 2'-(CH3)2CH(CH2)2θ2C-NHS0 2 - 2-Br 111 n-propyl ethyl 2'-(CH3)2CH(CH2)2θ2C-NHS0 - 2-Br 112 n-propyl ethyl 2'-(CH3)2CH(CH2)2θ2C-NHS0 2 - 2-Br 113 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 114 n-propyl ethyl Ph(CH )2θ2C-NHSθ2- 3-F 115 n-propyl ethyl Ph(CH 2 )3θ2C-NHSθ2- 3-F 116 n-propyl ethyl Ph(CH 2 ) 4 θ2C-NHS0 2 - 2-F 117 n-propyl ethyl CH3(CH2)3-NH-CO-NHSθ2- 2-F (CH3)2CH(CH2)2θ2C-NHS0 - 2-F (CH 3 )2CH(CH2)0 2 C-NHS02- 2-F (CH 3 )(CH )3θ2C-NHS0 2 - 2-F (CH3)(CH2)2θ 2 C-NHS0 2 - 2-F (CH3)2CH0 2 C-NHS0 2 - 2-F PhCH2θ 2 C-NHS0 2 - 2-F Ph(CH 2 )2θ C-NHSθ2- 3-F Ph(CH )3θ 2 C-NHS0 2 - 3-F 126 n-propyl ethyl Ph(CH 2 ) 4 0 2 C-NHS02- 2-F 127 n-propyl ethyl CH3(CH )3-NH-CO-NHS0 2 - 2-F 128 n-propyl ethyl (CH 3 )2CH(CH2)2θ2C-NHS0 - 2-F 129 n-propyl ethyl (CH 3 )2CH(CH2)0 2 C-NHS0 2 - 3-F 130 n-propyl ethyl (CH 3 )(CH2)3θ2C-NHS0 2 - 3-F 131 n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - 2-F 132 n-propyl ethyl (CH3)2CH0 2 C-NHS0 2 - 3-F 133 n-propyl ethyl PhCH2θ 2 C-NHS0 2 - H H H H 137 n-propyl ethyl CH3(CH2)3-NH-CO-NHS0 2 - 2-F 138 n-propyl ethyl H3)2CH(CH2)2θ2C- HS0 2 - 2-F 139 n-propyl ethyl or CONH 2 (CH 3 ) 2 CH(CH 2 )θ2C-NHSθ2- 2-F 140 n-propyl ethyl (CH3)(CH2)3θ2C-NHS0 2 - 2-CH 3 F 141 n-propyl ethyl (CH3)(CH2)2θ2C-NHSθ2- 2-F 142 n-propyl ethyl SO-CH 3 (CH3)2CH0 2 C-NHS0 - 2-F 143 n-propyl ethyl P CH2θ2C-NHSθ2- 2-F 144 n-propyl ethyl tu-ut- 3 ph(CH2)2θ C-NHS0 2 - 2-F 145 n-propyl ethyl Ph(CH 2 )3θ C-NHSθ2- 2-CI 146 n-propyl ethyl Ph(CH 2 ) 4 0 C-NHSθ2- H 147 n-propyl ethyl CH3(CH2)3-NH-CO-NHS0 - H 148 n-propyl ethyl OC NH-C ' F 3 (CH3)2CH(CH2)2θ2C- HS0 2 - 2-CH 2 CH 3 149 n-propyl ethyl (CH 3 )2CH(CH2)0 2 C-NHS02- 2-F 150 n-propyl ethyl (CH3)(CH2)3θ 2 C-NHS0 2 - H 151 n-propyl ethyl (CH3)(CH2)2θ 2 C-NHS0 - 2-Br 152 n-propyl ethyl (CH3)2CH0 2 C-NHS0 2 - 3-CH(CH 3 ) 2 153 n-propyl ethyl PhCH2θ C-NHS0 2 - 2-N0 2 154 n-propyl ethyl Ph(CH 2 )2θ2C-NHSθ2- H 155 n-propyl ethyl Ph(CH 2 )3θ C-NHSθ2- H 156 n-propyl ethyl Ph(CH 2 ) 4 θ2C-NHSθ2- H 157 n-propyl ethyl CH3(CH2)3-NH-CO-NHS02- 2-I 158 n-propyl ethyl (CH 3 )2CH(CH2)2θ2C-NHS0 2 - H 159 n-propyl ethyl (CH3)2CH(CH2)θ2C-NHS0 2 - H 160 n-propyl ethyl (CH3)(CH2)3θ2C-NHS0 - H 161 n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - 2-F 162 n-propyl ethyl (CH3) 2 CH0 2 C-NHS0 2 - 2-F 163 n-propyl ethyl PhCH 2 0 C-NHS02- 2-F 164 n-propyl ethyl Ph(CH2) 2 0 2 C-NHSθ2- 2-F 165 n-propyl ethyl Ph(CH 2 ) 3 0 C-NHS0 2 - 2-F 166 n-propyl ethyl Ph(CH 2 ) 4 0 2 C-NHS0 2 - H 167 n-propyl ethyl CH3(CH2)3-NH-CO-NHSθ2- H 168 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 - H 169 n-propyl ethyl (CH3)2CH(CH2)0 C-NHS0 2 - 2-F 170 n-propyl ethyl (CH3)(CH2)3θ C-NHS0 2 - 2-F 171 n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - 2-F 172 n-propyl ethyl (CH )2CH0 2 C-NHSθ2- 2-F 173 n-propyl ethyl PhCH2θ2C-NHSθ2- 2-F 174 n-propyl ethyl Ph(CH 2 )2θ2C-NHS0 2 - 2-F 175 n-propyl ethyl Ph(CH 2 )3θ 2 C-NHSθ2- H 176 n-propyl ethyl Ph(CH 2 ) 4 0 C-NHSθ2- 2-F 177 n-propyl ethyl CH3(CH2)3-NH-CO-NHS0 2 - 2-F 178 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 179 n-propyl ethyl (CH3)2CH(CH2)0 2 C-NHS0 2 - H 180 n-propyl ethyl (CH3)(CH2)3θ2C-NHSθ2- 2-CI 181 ethyl ethyl (CH3)2CH(CH2)0 C-NHS02- 2-F 182 ethyl ethyl (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 183 ethyl ethyl (CH 3 )2CH(CH )0 2 C-NHS0 2 - H 184 ethyl ethyl (CH3)2CH(CH2)θ2C-NHS0 2 - H 185 ethyl ethyl (CH3)(CH2)3θ 2 C-NHS0 2 - 2-F 186 ethyl ethyl (CH3)(CH2)3θ 2 C-NHS0 2 - 2-F 187 n-propyl ethyl (CH3)2CH(CH 2 )0 2 C-NHS0 2 - 2-F ee 188 n-propyl ethyl (CH3)(CH 2 ) 2 0 2 C-NHS0 - 2-F ff 189 n-propyl ethyl (CH3)2CH(CH2)0 C-NHS0 2 - 2-F gg 190 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F 191 n-propyl ethyl 192 n-propyl 2-F hh 193 n-propyl 2-F 194 n-propyl 2-F 195 n-propyl 2-F 196 n-propyl 2-F 197 n-propyl 2-F 198 n-propyl 2-F 199 n-propyl 2-F 200 n-propyl ethyl (CH 3 )2CH(CH2)2θ 2 C-NHS0 2 - 2-F 201 n-propyl ethyl (CH3)2CH(CH2)2θ C-NHS0 2 - 2-F 202 n-propyl ethyl (CH3)2CH(CH 2 )2θ2C-NHS0 2 - 2-F (M+H) + =791 203 n-propyl ethyl (CH 3 )2CH(CH )2θ2C-NHSθ2- 2-F 204 n-propyl ethyl (CH 3 ) 2 CH(CH 2 )2θ2C-NHSθ2- 2-F 205 n-propyl ethyl (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F 205 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F 206 n-propyl ethyl (M+H)+=769.5 a) 1 H NMR (K+ salt) (DMSO-dδ) δ 7.97-7.30 (m, 13H); 7.04 (d, 1H, J=8 Hz); 6.78 (d, 2H, J=8 Hz); 5.43 (S, 2H); 5.29 (S,2H); 3.11 (S. 3H); 2.70-2.45 (m, 4H); 1.60 (t of q, 2H, J=7,7 Hz); 0.99 (t, 3H, J=7 Hz); 0.87 (t, 3H, J=7 Hz). b) 1 H NMR (K+ salt) (DMSO-d6) δ 7.97-7.00 (m, 6H); 6.77 (d, 2H, J=8 Hz); 5.41 (s, 2H); 5.28 (S. 2H); 3.74 (t, 2H, J=7 Hz); 2.75-2.45 (m, 6H); 1.60 (t of q, 2H, J=7,7 Hz); 0.98 (t, 3H, J=7 Hz); 0.87 (t, 3H, J=7 Hz). c) 1 H NMR (K+ salt) (DMSO-d 6 ) δ 8.14 (d, 1H, J=8 Hz); 7.73 (d, 2H, J=8 Hz); 7.60-7.42 ( , 3H); 7.42-7.20 (m, 8 H); 7.08 (d, 1H, J=8 Hz); 6.80 (d, 2H, J=8 Hz); 5.38 (S, 4H); 3.76 (t, 2H, J=7 Hz); 2.63 (q, 2H, J= 7 Hz); 2.57 (t, 2H, J=7 Hz); 1.66 (t of q, 2H, J=7,7 Hz); 1.50-1.10 (m, 3H); 1.05 (t, 3H, J=7 Hz); 0.91 (t, 3H, J=7 Hz). d) 1 H NMR (K+ salt) (CDCI3) δ 8.07 (d, 1 H, J=8 Hz); 7.74 (d, 2H, J=8 Hz); 7.60-7.00 (m, 14H); 7.00 (d, 3H, J=8Hz); 6.31 (t, 1H, J=8 Hz); 5.38 (S, 2H); 5.31 (S, 2H); 3.89 (t, 2H, J=7 Hz); 2.75 (q, 4H, J=7Hz); 2.45 (t, 2H, J=7 Hz); 1.65 (t of q, 2H, J=77 Hz); 1.06 (t, 3H, J=7 Hz); 0.90 (t, 3H, J=7 Hz). e) 1 H NMR (K+ salt) (CDCI3) δ 8.08 (d, 1 H, J=8 Hz); 7.75 (d, 2H, J=8 Hz); 7.60-7.43 (, 3H); 7.43-6.95 (m, 9H); 6.36 (t, 1 H, J=8 Hz); 5.40 (S. 2H); 5.37 (s, 2H); 3.63 (t, 2H, J=7 Hz); 2.66 (q, 2H, J=7 Hz); 2.56 (t, 2H, J=7 Hz); 1.64 (t of q, 2H, J=7,7 Hz); 1.50-1.20 (m, 2H); 1.07 (t, 3H, J=7 Hz); 0.91 (t, 3H, J=7 Hz); 0.67 (t, 3H, J=7 Hz). f) 1 H NMR (CDCI3) δ 8.27 (d, 1H, J=8 Hz); 7.77 (d, 2H, J=8 Hz); 7.70-7.00 (m, 2H); 6.73 (t, 1 H, J=8 Hz); 5.57 (S. 2H); 5.46 (s, 2H); 3.78 (d, 2H, J=7 Hz); 3.00-2.75 (m, 4H); 1.90 (m, 3H); 1.20 (t, 3H, J=7 Hz); 1.00 (t, 3H, J=7 Hz); 0.77 (d, 6H, J=7 Hz). g) 1 H NMR (K+ salt) (CDCI3) δ 8.08 (d, 1H, J=8 Hz); 7.75 (d, 2H, J=8 Hz); 7.65-7.00 (m, 12H); 6.36 (t, 1H, J=8 Hz); 5.41 (s, 2H); 5.36 (s, 2H); 3.68 (t, 2H, J=7 Hz); 2.65 (q, 2H, J=7 Hz); 2.56 (t, 2H, J=7 Hz); 1.66 (t of q, 2H, J= 7,7 Hz); 1.45-0.95 (m, 7H); 0.91 (t, 3H, J=& Hz) h) 1 H NMR (K+ salt) (CDCI3) δ 8.04 (d, 1 H, J=8 Hz); 7.41 (d, 1H, J=8 Hz); 7.40-6.95 (m, 10H); 6.91 (d, 2H, J=8 Hz); 6.84 (d, 1 H, J=8 Hz); 6.47 (t, 1 H, J=8 Hz); 5.38 (s, 2H); 5.28 (S. 2H); 3.68 (t, 2H, J=7 Hz); 2.82 (q, 2H, J=7 Hz); 2.59 (t, 2H, J=7 Hz); 1.71 (t of q, 2H, J=7, & Hz); 1.32 (t of t, 2H, J=7, 7 Hz); 1.25-1.00 (m, 5H); 0.94 (t, 3H, J=7 Hz); 0.74 (t, 3H, J=7 Hz). i) 1 H NMR (K+ salt) (CDCI 3 ) δ 8.07 (d, 2H, J=8 Hz); 7.85 (d, 2H, J=8 Hz); 7.65-7.15 (m, 10H); 7.10 (d, 1H- J=8 Hz); 7.05-6.90 (m, 1H); 6.50-6.35 (m, 1H); 5.51 (s, 2H); 5.37 (s, 2H); 3.70-3.55 ( , 2H); 2.74 (q, 2H, J=7 Hz); 2.62 (t, 2H, J=7 Hz); 1.73 (t of q, 2H, J=7,7 Hz); 1.45-1.20 (m, 2H); 1.15 (t, 3H, J=7 Hz); 0.96 (t, 3H, J=7 Hz); 0.68 (t, 3H, J=7 Hz). j) 1 H NMR (K+ satt) (CDCI3) δ 8.07 (d, 2H, J=8 Hz); 7.85 (d, 2H, J=8 Hz); 7.60-7.10 (m, 9H); 7.07 (d, 1H, J=8 Hz); 6.95 (d, 1 H, J=8 Hz); 6.41 (t, 1H, J=8 Hz); 5.52 (s, 2H); 5.37 (s, 2H); 3.69 (t, 2H- J=7 Hz); 2.72 (q, 2H, J=7 Hz); 2.62 (t, 2H, J=7 Hz); 1.71 (t of q, 2H, J=7,7 Hz); 1.50-1.30 (m, 1H); 1.30-1.10 (m, 2H); 1.13 (t, 3H, J=7 Hz); 0.96 (t, 3H, J=7 Hz); 0.71 (d, 6H, J=7 Hz). k) 1 H NMR (K+ salt) (CDCI3) δ 8.05-7.90 (m, 1H); 7.50-6.90 (m, 12H); 6.46 (t, 1 H, J=8 Hz); 5.37 (s, 2H); 5.18 (s, 2H); 3.75-3.40 (m, 2H); 2.72 (q, 2H, J=7 Hz); 2.60-2.40 (m, 2H); 1.75-1.50 (m, 2H); 1.50-1.20 (m, 2H); 1.20-1.00 (m, 3H); 0.95-0.75 (m, 3H); 0.75-0.60 (m, 3H). I) 1 H NMR (K+ salt) (CDCI3) δ 8.05-7.90 (m, 1 H); 7.50-6.90 (m, 12H); 6.60-6.40 (m, 1 H); 5.42 (s, 2H); 5.25 (s, 2H); 3.90-3.60 (m, 2H); 2.77 (q, 2H, J=7 Hz); 2.70-2.50 (m, 2H); 1.80-1.55 (m, 2H); 1.55-1.30 (m, 1 H); 1.35-1.10 (m, 5H); 1.00-0.80 (m, 3H); 0.76 (d, 6H, J=7 Hz). m) 1 H NMR (K+ salt) (CDCI3) δ 8.00 (d, 1H, J=8 Hz); 7.50-6.95 (m, 12H); 6.60-6.40 (m, 1H); 5.41 (s, 2H); 5.20 (s, 2H); 3.70-3.50 (m, 2H); 2.77 (q, 2H, J=7 Hz); 2.59 (t, 2H, J=7 Hz); 1.70 (m, 2H); 1.45-1.00 (m, 2H); 1.13 (t, 3H, J=7 Hz); 0.94 (t, 3H, J=7 Hz); 0.80-0.50 (m, 3H). n) 1 H NMR (K+ salt) (CDCI 3 ) δ 7.97 (d, 1 H, J=8 Hz); 7.50-6.90 (m, 12 H); 6.55-6.40 (m, 1H); 5.40 (s, 2H); 5.21 (s, 2H); 3.80-3.60 (m, 2H); 2.77 (q, 2H, J=7 Hz); 2.60 (t, 2H, J=7 Hz); 1.71 -1.30 (m, 1H); 1.30-1.00 (m, 2H); 1.13 (t, 3H, J=7 Hz); 0.96 (t, 3H, J=7 Hz); 0.75 (d, 6H, J=7 Hz). o) H NMR (K+ salt) (CDCI 3 ) δ 7.98 (d, 1 H, J=8 Hz); 7.46 (d, 1 H, J=8 Hz); 7.45-7.10 (m, 11H); 7.07 (d, 1H, J=8 Hz); 6.98 (d, 1H, J=8 Hz); 6.46 (t, 1H, J=8 Hz); 5.38 (s, 2H); 5.15 (s, 2H); 3.60 (t, 2H, J=7 Hz); 2.77 (q, 2H, J=7 Hz); 2.59 (t, 2H, J=7 Hz); 1.71 (t of q, 2H, J=7,7 Hz); 1.34 (t of q, 2H, J=7,7 Hz); 1.15 (t, 3H, J=7 Hz); 0.95 (t, 3H, J=7 Hz); 0.67 (t, 3H, J=7 Hz). p) 1 H NMR (K+ salt) (CDCI3) δ 7.98 (d, 1 H, J=8 Hz); 7.46 (d, 1H, J=8 Hz); 7.45-7.10 (m, 11H); 7.08 (d, 1H, J=8 Hz); 7.01 (d, 1 H, J=8 Hz); 6.47 (t, 1 H, J=8 Hz); 5.38 (s, 2H); 5.17 (S, 2H); 3.73 (t, 2H, J=7 Hz); 2.77 (q, 2H, J=7 Hz); 2.59 (t, 2H, J=7 Hz); 1.80-1..60 (m, 2H); 1.50-1.30 (m, 1H); 1.30-1.10 (m, 2H); 1.15 (t, 3H, J=7 Hz); 0.90 (t, 3H, J=7 Hz); 0.74 (d, 6H, J=7 Hz). q) 1 H NMR (K+ salt) (CDCI3) δ 9.13 (s, 1 H); 8.69 (s. 2H); 7.98 (S, 1 H, J=8 Hz); 7.60-7.40 (m, 3H); 7.34 (t, 1H, J=8 Hz); 7.30-7.10 (m, 4H); 7.09 (d, 1H, J=8 Hz); 7.02 (d, 1 H, J=8 Hz); 6.45 (t, 1H, J=8 Hz); 6.45 (t, 1H, J=8 Hz); 5.36 (S, 2H); 5.18 (s, 2H); 3.56 (t, 2H, J=7 Hz); 2.73 (q, 2H, J=7 Hz); 2.60 (t, 2H, J=7 Hz); 1.71 (t of q, 2H, J=7J Hz); 1.32 (t of q, 2H, J=7,7 Hz); 1.13 (t, 3H, J=7 Hz); 0.94 (t, 3H, J=7 Hz); 0.67 (t, 3H, J=7 Hz). r) 1 H NMR (K+ salt) (CDCI 3 ) δ 8.07 (d, 1 H, J=8 Hz); 7.45-7.15 (m, 5H); 7.14 (d, d, 1 H, J=8 Hz); 7.03 (d, 1 H, J=8 Hz); 6.93 (t, 1 H, J=8 Hz); 6.86 (d, 2H, J=8 Hz); 6.47 (t, 1 H, J=8 Hz); 5.40 (S. 2H); 4.30-4.15 (m, 2H); 4.00-3.85 (m, 2H); 3.76 (t, 2H, J=7 Hz); 2.89 (q, 2H, J=7 Hz); 2.64 (t, 2H, J=7 Hz); 1.90-1.60 (m, 4H); 1.60-1.30 (m, 1 H); 1.35-1.20 (m, 5H); 0.97 (t, 3H, J=7 Hz); 0.77 (d, 6H, J=7 Hz). S) 1 H NMR (CDCI3) δ 8.26 (d, 1H, J=8 Hz); 7.64 (t, 1 H, J=8 Hz); 7.57 (t, 1H, J=8 Hz); 7.40-7.20 (m, 4H); 7.10 (d, 1H, J=11 Hz); 7.05-6.80 (m, 4H); 6.64 (t, 1H, J=8 Hz); 5.57 (s, 2H); 4.40 (t, 2H, J=7 Hz); 4.15-3.95 (m, 4H); 2.91 (q, 2H, J=7 Hz); 2.66 (t, 2H, J=7 Hz); 2.17 (t Of t, 2H, J=7,7 Hz); 1.74 (t of q, 2H, J=7,7 Hz); 1.55-1.25 (m, 3H); 1.27 (t, 3H, J=7 Hz); 0.98 (t, 3H, J=7 Hz); 0.82 (d, 6H, J=7 Hz). t) 1 H NMR (CDCI 3 ) δ 8.19 (d, 1H. J=8 Hz); 7.60-7.40 (m, 2H); 7.30-7.10 (m, 6H); 7.04 (d, 1H, J=11 H); 6.90 (d. 1H, J=8 Hz); 6.53 (t, 1H, J=8 Hz); 5.48 (S, 2H); 4.43 (S, 2H); 4.21 (t, 2H, J=7 Hz); 3.93 (t, 2H, J_=7 Hz); 3.46 (t, 2H, J=7 Hz); 2.82 (q, 2H, J=7 Hz); 2.59 (t, 2H, J=7 Hz); 1.97 (t Of t, 2H, J=7,7 Hz); 1.66 (t of q, 2H, J=7,7 Hz); 1.50-1.00 (m, 6H); 0.89 (t, 3H, J=7 Hz); 0.74 (d, 6H, J=7 Hz). u) H NMR (CDCI3) δ 8.16 (d, 1H, J=8 Hz); 7.77 (d, 2H, J=8 Hz); 7.70-7.20 (m, 13H); 6.93 (d, 2H, J=8 Hz); 5.96 (t, 1H, J=8 Hz); 5.41 (s, 2H); 5.37 (s, 2H); 3.03 (q, 2H, J=7 Hz); 2.74 (q, 2H, J=7 Hz); 2.63 (t, 2H, J=7 Hz); 1.69 (t of q, 2H, J=7,7 Hz); 1.40-1.00 (m, 7H); 0.95 (t, 3H, J=7 Hz); 0.81 (t, 3H, J=7 Hz). v) 1 H NMR (K+ salt) (CDCI3) δ 8.07 (d, 1 H, J=8 Hz); 7.75 (d, 2H, J=8 Hz); 7.59 (d, 1H, J=8 Hz); 7.60-7.00 (m, 11 H); 6.37 (t, 1H, J=8 Hz); 5.46 (s, 2H); 5.38 (s, 2H); 3.67 (t, 2H, J=7 Hz); 2.56 (t, 2H, J=7 Hz); 1.63 (t of t, 2H, J=7,7 Hz); 1.50-1.10 (m, 5H); 0.86 (t, 3H, J=7 Hz); 0.70 (d, 6H, J=7 Hz). w) 1 H NMR (CDCI 3 ) δ 8.18 (d, 1 H, J=8Hz); 7.65-7.05 (m, 12H); 7.01 (d, 1H, J=10 Hz); 6.91 (d, 1H, J=8 Hz); 6.57 (t, 1H, J=8 Hz); 5.51 (s, 2H); 5.33 (s, 2H); 3.96 (t, 2H, J=7 Hz); 2.84 (q, 2H, J=7 Hz); 2.58 (t, 2H, J=7 Hz); 1.66 (q, 2H, J=7 Hz); 1.50-1.20 (m, 3H); 1.16 (T, 3H, J=7 HZ); 0.90 (T, 3H, J=7 HZ); 0.74 (d, 6H, J=7 Hz). x) 1 H NMR (DMSO-d 6 ) δ 7.74 (s, 1 H); 7.80-7.35 (m, 12H); 6.98 (d, 2H, J-8 Hz); 6.83 (d, 2H, J=8 Hz); 5.48 (S, 2H); 5.29 (s, 2H); 2.72 (q 2H, J=7 Hz); 2.52 (t, 2H, J=7 Hz); 1.54 (t of q, 2H, J=7,7 Hz); 1.05 (t, 3H, J=7 Hz); 0.83 (t, 3H, J=7 Hz). y) 1 H NMR (CDCI 3 ) δ 7.77 (d, 1H, J8 Hz); 7.60 (t, 1H, J=8 Hz); 7.51 (t, 1H, J=8 Hz); 7.45- 7.00 (m, 6H); 7.09 (d, 6H, J=8 Hz); 6.83 (d, 1H, J=11 Hz); 6.72 (d, 1H, J=8 Hz); 6.30 (t, 1H, J=8 Hz); 5.41 (s, 2H); 5.12 (s, 2H); 2.70 (q, 2H, J=7 Hz); 2.44 (t, 2H, J=7 Hz); 1.60 (t of q, 2H, J=7,7 Hz); 1.04 (t, 3H, J=7 Hz); 0.86 (t, 3H, J=8 Hz). z) 1 H NMR (CDCI 3 ) δ 7.85 (d, 1H, J=7 Hz); 7.67 (d, 2H, J=7 Hz); 7.65-7.20 (m, 10H); 6.91 (d, 2H, J=7 Hz); 6.55 (d, 2H, J=7 Hz); 5.26 (s, 2H); 5.21 (s, 2H); 2.50-2.25 (m, 2H); 2.20-2.00 (m, 2H); 1.65-1.40 ( , 2H); 0.90-0.60 (m, 6H). aa) 1 H NMR (CDCI 3 ) δ 7.85-7.70 (m, 1H); 7.65-7.40 (m, 2H); 7.41 (d, 1H, J=8 Hz); 7.40- 6.80 (m, 11H); 6.75-6.60 (m, 2H); 5.38 (bs, 2H); 5.25-5.10 (m, 2H); 4.73 (s, 1H); 4.41 (s, 1H); 3.50-3.30 (m, 1H); 3.20-3.00 (m, 1H); 2.70-2.55 (m, 2H); 2.40-2.25 (m, 2H); 1.70-0.60 (m, 15H). bb) 1 H NMR (CDCI3) δ 7.95-7.80 (m, 1H-); 7.60-7.20 (m, 12H); 7.04 (d, 2H, J=8 Hz); 6.67 (d, 2H, J=8 Hz); 5.38 (s, 2H); 5.16 (S. 2H); 2.45 (q, 2H, J=7 Hz); 2.15 (t, 2H, J=7 Hz); 1.57 (t of q, 2H, J=7,7 Hz); 0.90-0.70 (m, 6H). CC) 1 H NMR (CDCl3) δ 7.85 (d, 1H, J=8 Hz); 7.70-7.50 (m, 2H); 7.45-7.10 (m, 10H); 6.97 (d, 2H, J=8 Hz); 6.54 (d, 2H, J=8 Hz); 5.30 (S, 2H); 5.07 (s, 2H); 2.45-2.25 (m, 2H); 2.20- 2.00 (m, 2H); 1.54 (t of q, 2H, J=7,7 Hz); 0.83 (t, 3H, J=7 Hz); 0.73 (t, 3H, J=7 Hz). dd) 1 H NMR (CDCl3) δ 7.83 (d, 1H, J=7 Hz); 7.68 (d, 2H, J=7 Hz); 7.60-7.10 (m, 10 H); 6.80-6.60 (m, 2H); 6.27 (t, 1 H, J=7 Hz); 5.30 (s, 4H); 2.50 (m, 2H); 2.33 (t, 2H, J=7 Hz); 1.54 (t of q, 2H, J=7,7 Hz); 0.95-0.60 (m, 6H). ee) 1 H NMR (K+ salt) (CDCI3) δ 8.01 (d, 1H, J=8 Hz); 7.85-7.65 (m, 4H); 7.65-7.50 (m, 2H); 7.50-7.12 (m, 6H); 7.09 (d, 1H, J=8 Hz); 7.00 (d, 1H, J=8 Hz); 6.48 (t, 1H, J=8 Hz); 5.42 (s, 2H); 5.27 (s, 2H); 3.70 (t, 2H, J=7 Hz); 2.84 (q, 2H, J=7 Hz); 2.63 (t, 2H, J=7 Hz); 1.73 (t Of q, 2H, J=7, 7 Hz); 1.50-1.30 (m, 1H); 1.30-1.10 (m, 5H); 0.96 (t, 3H, J=7 Hz); 0.71 (d, 6H, J=7 Hz). ff) 1 H NMR (K+ salt) (CDCfc) δ 7.93 (d, 1H, J=8 Hz); 7.80-7.60 (m, 4H); 7.47 (t, 2H, J=8 Hz); 7.45-7.05 (m, 6H); 7.01 (d, 1 H, J=8 Hz); 6.93 (d, 1H, J=8 Hz); 6.40 (t, 1 H, J=8 Hz); 5.34 (s, 2H); 5.19 (s, 2H); 3.53 (t, 2H, J=7 Hz); 2.77 (q, 2H, J=7 Hz); 2.57 (t, 2H, J=7 Hz); 1.80-1.50 (m, 2H); 1.35-1.10 (m, 2H); 1.08 (t, 3H, J=7 Hz); 0.88 (t, 3H, J=7 Hz); 0.60 (t, 3H, J=7 Hz). gg) 1 H NMR (K + salt) (CDCI3) δ 8.03 (d, 1H, J=8 Hz); 7.40-7.15 (m, 5H); 7.10 (d, 1H, J=8 Hz); 7.06 (d, 1H, J=8 Hz); 6.95-6.80 (m, 2H); 6.51 (t, 1H, J=8 Hz); 5.44 (s, 2H); 5.25 (s, 2H); 3.97 (t, 2H, J=7 Hz); 3.76 (t, 2H, J=7 Hz); 2.82 (q, 2H, J=7 Hz); 2.61 (t, 2H, J=7 Hz); 1.90-1.55 (m, 5H); 1.55-1.35 (m, 1H); 1.28 (q, 2H, J=7 Hz); 1.14 (t, 3H, J=7 Hz); 0.94 (t, 3H, J=7 Hz); 0.92 (d, 6H, J=7 Hz); 0.77 (d, 6H, J=7 Hz). hh) -H NMR (K+ salt) (CDCI3) δ 8.00 (d, 1H, J=8 Hz); 7.80 (d, 2H, J=8 Hz); 7.45 (t, 1H, J=8 Hz); 7.40-7.05 (m, 5H); 7.05 (d, 1H, J=8 Hz); 7.00 (d, 1H, J=8 Hz); 6.47 (t, 1H, J=8 Hz); 5.37 (s, 2H); 4.18 (t, 2H, J=7 Hz); 3.63 (t, 2H, J=7 Hz); 2.97 (t, 2H, J=7 Hz); 2.81 (q, 2H, J=7 Hz); 2.55 (t, 2H, J=7 Hz); 2.10-1.90 (m, 2H); 1.80-1.50 (m, 2H); 1.50-1.20 (m, 1H); 1.25-1.10 (m, 5H); 0.87 (t, 3H, J=7 Hz); 0.66 (d, 6H, J=7 Hz). The following examples in Table 2 can be synthesized by the procedures described in examples 1-12 and by methods familiar to one skilled in the art. Table 2. Ex R6 R8 Ra Rb R13 R2 m. p. n-propyl ethyl H CH 3 (CH2)3θ2C-NHSθ2- 2-CI 16 n-propyl ethyl H CH3(CH2)3θ2C-NHS0 2 - 2-F 217 n-propyl ethyl H CH3(CH2)3θ 2 C-NHS0 2 - 2-CI 218 n-propyl ethyl H CH3(CH2)3θ C-NHSθ2- 2-CI 219 n-propyl ethyl H CH 3 (CH2)2θ 2 C-NHS0 2 - 2-F 220 n-propyl ethyl H (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 221 n-prop l ethyl H CH 3 (CH2)2θ2C-NHS0 2 - 2-F 222 n-propyl ethyl H (CH3)2CH(CH 2 )2θ2C-NHS0 2 - 2-F 223 n-propyl ethyl H CH 3 (CH2)2θ 2 C-NHS0 2 - 2-F 224 n-propyl ethyl H (CH3) 2 CH(CH2)2θ2C-NHS0 2 - 2-F (M+H) + =757 225 n-propyl ethyl CH 3 (CH2)2θ 2 C-NHS0 2 - 2-F 226 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F 227 n-propyl ethyl CH 3 (CH2)2θ 2 C-NHS0 2 - 2-F 228 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F 229 n-propyl ethyl (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F 230 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F 231 n-propyl ethyl (CH3(CH 2 )3-NH-CO-NHS0 - 2-F 232 n-propyl CI (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F -CH 5 233 n-propyl ethyl ύco* (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F 234 n-propyl ethyl 235 n-propyl ethyl 236 n-propyl ethyl 237 n-propyl ethyl 238 n-propyl ethyl 239 n-propyl ethyl 240 n-propyl ethyl 241 n-propyl ethyl 242 n-propyl ethyl 243 n-propyl ethyl 244 n-propyl ethyl H (CH 3 )2CH(CH2)2θ2C-NHS0 - H 245 n-propyl ethyl (CH3)2CH(CH 2 )θ2C-NHS0 - H 246 n-propyl ethyl (CH3)(CH2)3θ C-NHSθ2- H 247 n-propyl ethyl (CH3)(CH2)2θ2C-NHS0 2 - H 248 n-propyl ethyl (CH3)2CHθ2C-NHS0 - H 249 n-propyl ethyl PhCH2θ 2 C-NHS0 2 - H 250 n-propyl ethyl CH3(CH 2 )3-NH-CO-NHS0 2 - 2-F 251 n-propyl ethyl (CH3)2CH(CH2)2θ 2 C-NHS0 2 - 2-F 252 n-propyl ethyl (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 253 ethyl ethyl CH 3 (CH2)2θ C-NHSθ2- 2-F 254 ethyl ethyl H (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F 255 ethyl CI H CH 3 (CH2)2θ2C-NHSθ2- 2-F 256 ethyl Br H (CH 3 )2CH(CH2)2θ 2 C-NHSθ2- 2-F 257 ethyl C2F5 CH3 CH 3 (CH2)2θ2C-NHSθ2- 2-F 258 ethyl ethyl n-butyl (CH3)2CH(CH2)2θ2C-NHS0 - H 259 n-propyl ethyl H CN 4 H 2-F 260 ethyl ethyl H (CH3)2CH(CH )2-NH-CO-NHS0 2 - 2-F 261 n-propyl ethyl H (CH3)2CH(CH2)2θ 2 C-NHS0 2 - 2-F 262 n-propyl ethyl H (CH3)2CH(CH2)θ2C-NHSθ2- 2-F 263 n-propyl ethyl H (CH3)(CH2)2θ2C-NHSθ2- 2-F 264 n-propyl ethyl H (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 265 n-propyl ethyl H (CH3)2CH(CH2)0 C-NHSθ2- 2-F 266 n-propyl ethyl H (CH3)(CH2) 2 0 2 C-NHS0 2 - 2-F 267 n-propyl ethyl H (CH3)2CH(CH2) 2 0 2 C-NHS0 2 - 2-F 268 n-propyl ethyl H (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 269 n-propyl ethyl H (CH3)(CH2)2θ 2 C-NHSθ2- 2-F 270 n-propyl ethyl H (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 271 n-propyl ethyl H (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 272 n-propyl ethyl H (CH3)(CH2)2θ2C-NHSθ2- 2-F 273 n-propyl ethyl H (CH3)2CH(CH2)2θ 2 C-NHS0 2 - 2-F 274 n-propyl ethyl H (CH 3 )2CH(CH2)0 2 C-NHSθ2- 2-F 275 n-propyl ethyl H (CH 3 )(CH2) 2 0 2 C-NHS0 2 - 2-F 276 n-propyl ethyl H (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F 277 n-propyl ethyl H (CH 3 ) CH(CH2)0 2 C-NHS0 2 - 2-F 278 n-propyl ethyl H (CH 3 )(CH 2 )2θ 2 C-NHS0 2 - 2-F 279 n-propyl ethyl H (CH3)2CH(CH2)2θ 2 C-NHS0 2 - 2-F 280 n-propyl ethyl H (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 281 n-propyl ethyl H (CH3)(CH2)2θ C-NHS0 2 - 2-F 282 n-propyl ethyl H CN 4 H 2-F 283 n-propyl ethyl CH 3 (CH3)2CH(CH )2θ C-NHSθ2- 2-F 284 n-propyl ethyl n-C3H 7 (CH3)2CH(CH2)2θ 2 C-NHS0 2 - 2-F 285 n-propyl ethyl H (CH3)2CH(CH2) 2 0 2 C-NHS0 2 - 2-F 286 n-propyl ethyl 287 n-propyl ethyl (M+H) + =703. 288 n-propyl ethyl 2-F 289 n-propyl ethyl 2-F 290 n-propyl ethyl 2-F 291 n-propyl ethyl 2-F 292 n-propyl ethyl 2-F 293 n-propyl ethyl 2-F 294 n-propyl ethyl 2-F 295 n-propyl ethyl 2-F 296 n-propyl ethyl 2-F 297 n-propyl ethyl H (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F 298 n-propyl ethyl H (CH3)2CH(CH2)θ2C-NHSθ2- 2-F 299 n-propyl ethyl HH (CH3)(CH2)2θ 2 C-NHS0 2 - 2-F 300 n-propyl ethyl H CN 4 H 2-F 301 n-propyl ethyl H (CH3)2CH(CH2) 2 0 2 C-NHS0 2 - 2-F 302 n-propyl ethyl H (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 303 n-propyl ethyl H (CH3)(CH2) 2 0 2 C-NHS0 2 - 2-F 304 n-propyl ethyl H CN 4 H 2-F 305 n-propyl ethyl H (CH3)2CH(CH2)2θ 2 C-NHS0 2 - 2-F 306 n-propyl ethyl H (CH3)2CH(CH2)0 2 C-NHS0 2 - 2-F 307 n-propyl ethyl H (CH 3 )(CH )2θ 2 C-NHS0 2 - 2-F (M+H) + =665. 323 n-propyl ethyl H (CH 3 ) 2 CH(CH 2 )2θ 2 C-NHS0 2 - 2-F 324 n-propyl ethyl (M+H)+=693 326 n-propyl ethyl -NH JC" N3 H (CH 3 )2CH(CH2)2θ2C-NHS0 2 - 2-F The following examples in Table 3 can be synthesized by the procedures described in examples 1 -12 and by methods familiar to one skilled in the art. Table 3. Ex R6 R8 Ra R13 R2 m.p. n-propyl ethyl (CH3) 2 CH(CH 2 )2θ2C-NHSθ2- 2-F 340 n-propyl ethyl (CH 3 )2CH(CH 2 ) 2 θ2C-NHSθ2- 2-F 341 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 342. n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 343 n-propyl ethyl (CH 3 )2CH(CH2)2θ2C-NHSθ2- 2-F 345 n-propyl ethyl (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F 346 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 347 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F 348 n-propyl ethyl (CH3)2CH(CH )2θ2C-NHSθ2- 2-F 349 n-propyl ethyl (CH 3 )2CH(CH 2 )2θ2C-NHS0 2 - 2-F 350 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 351 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 352 n-propyl ethyl (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F 353 n-propyl ethyl (CH3) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F 354 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 355 n-propyl ethyl (CH 3 )2CH(CH ) 2 02C-NHS0 2 - 2-F 356 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 357 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 358 n-propyl ethyl (CH3) 2 CH(CH 2 )2θ2C-NHSθ2- 2-F 359 n-propyl ethyl (CH 3 )2CH(CH 2 )2Q2C-NHS02- 2-F 360 n-propyl ethyl (CH3)2CH(CH2)2θ2C-NHS0 2 - 2-F 361 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F 362 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 363 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F 364 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 0 2 C-NHS0 - 2-F 365 n-propyl ethyl (CH 3 )(CH 2 )3θ 2 C-NHS0 2 - 2-F (M+H)+ M+H+ =720.3 366 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 Q2C-NHS0 2 - 2-F 367 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 368 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 369 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 Q2C-NHS0 2 - 2-F 370 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 371 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS02- 2-F Ph -CHJCHJ— N 372 n-propyl ethyl CO-CH 2 CH 2 CH 3 CH 3 (CH 2 ) 3 0C-NHS0 2 - 2-F Ph -CH 2 CH 2 — N s 373 n-propyl ethyl CO-Ph (CH 3 ) 2 CH(CH 2 ) 2 0C-NHS0 - 2-F / Ph -CH 2 CH 2 — ^ 374 n-propyl ethyl CO-Ph CH 3 (CH 2 ) 3 0 2 C-NHS0 2 - 2-F -CH 2 CH 2 — N^ 375 n-propyl ethyl CO-Ph CH 3 (CH 2 ) 2 OC-NHS0 2 - 2-F 376 n-propyl ethyl CH 3 (CH 2 ) 3 OC-NHS0 2 - 2-F CH2CH2CH3 -CH 2 CH 2 — N 377 n-propyl ethyl co-αv^wy, (CH 3 ) 2 CH(CH 2 ) 2 OC-NHS0 2 - 2-F -CH 2 CH 2 — N^ 378 n-propyl ethyl C0*Ph CH 3 (CH 2 ) 3 OC-NHS0 2 - 2-F 379 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 380 n-propyl ethyl (CH3) 2 CH(CH 2 )2θC-NHSθ2- 2-F ^Ha- -CH 2 CH 2 — N 381 n-propyl ethyl CH0 (CH 3 ) 2 CH(CH 2 ) 2 OC-NHS0 2 - 2-F 382 n-propyl ethyl 2-F +H) + =726.5 383 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 384 n-propyl ethyl (M+H)+=726.2 385 n-propyl ethyl (CH 3 )(CH2)2θ2C-NHS0 2 - 2-F (M+H)+=712.3 386 ethyl ethyl (CH 3 )(CH 2 ) 2 θ2C-NHS0 2 - 2-F 387 n-butyl CI (CH 3 )(CH 2 )2θ2C-NHSθ2- 2-F 388 n-propyl Br (CH 3 )(CH2) 2 0 C-NHS0 2 - 2-F 389 n-propyl N0 2 2-F 390 n-propyl CF 2 C 2-F 391 n-propyl CH3 (CH 3 )(CH 2 )2θ2C-NHSθ2- 2-F CO-Ph -CH 2 CH 2 — N 392 n-propyl ethyl CHjCHjCHjCHa (CH 3 )(CH 2 )3θC-NHSθ2- 2-F 393 n-propyl ethyl (CH 3 )(CH 2 )3θC-NHS0 2 - 2-F / CO-CH 2 CH 2 CH 2 CH 3 •CH 2 CH 2 — N. 394 n-propyl ethyl CH 2 CH 2 CH 3 (CH 3 )(CH2)3θC-NHS0 2 - 2-F 395 n-propyl ethyl -CN 4 H 2-F ^O-C^CHzCHs -CHaCH 2 — N 396 n-propyl ethyl Ph -CN H 2-F 397 n-propyl ethyl (CH 3 )(CH 2 ) 3 OC-NHS0 2 - 2-F 398 n-propyl ethyl (CH 3 )(CH ) 3 OC-NHS0 2 - 2-F The following examples in Table 4 can be synthesized by the prodedures described in examples 1-12 and by the synthetic schemes described herein and by methods familiar to one skilled in the art. Table 4. Ex R6 R8 Ra R 13 R2 X m.p. 408 n-propyl ethyl -CN 4 H 2-F -CO-NH- 409 n-propyl ethyl -CN H 2-F -O- 410 n-propyl ethyl (CH3) 2 CH(CH2)2θ2C-NHSθ2- 2-F -S- 411 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F -CH 2 - 412 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHSθ2- 2-F -CO- 413 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F -NMe- 414 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F -S0 2 - 415 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F -SO- 416 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F -NHCO- 417 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F -OCH 2 - 418 n-propyl ethyl (CH3)2CH(CH 2 )2θ2C-NHS0 2 - 2-F -CH 2 0- 419 n-propyl ethyl (CH3)2CH(CH 2 )2θ2C-NHSθ2- 2-F -SCH 2 - 420 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHS0 2 - 2-F -CH 2 S- 421 n-propyl ethyl (CH 3 ) 2 CH(CH ) 2 θ2C-NHSθ2- 2-F -NMeCH 2 - 422 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 - 2-F -NHS0 2 - 23 n-propyl ethyl (CH3) CH(CH 2 ) 2 C2C-NHS0 2 - 2-F -S0 2 NH- 24 n-propyl ethyl (CH3) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F -CH=CH- 425 n-propyl ethyl (CH 3 ) 2 CH(CH 2 )2θ 2 C-NHS0 2 - 2-F -CH(OPh)- 426 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 427 n-propyl ethyl (CH3)2CH(CH 2 )2θ2C-NHSθ2- 2-F -0- 428 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 - 2-F -CO- 429 n-propyl ethyl (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F -C(CH 3 ) 2 - 430 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHS02- 2-F 431 n-propyl ethyl (CH 3 ) 2 CH(CH ) 2 O2C-NHS0 2 - 2-F 432 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F 433 n-propyl ethyl (CH3)2CH(CH 2 )2θ2C-NHSθ2- 2-F 434 n-propyl ethyl (CH 3 )2CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 435 n-propyl ethyl (CH 3 )2CH(CH2)2θ2C-NHS0 2 - 2-F 436 n-propyl ethyl (CH 3 ) 2 CH(CH2)2θ2C-NHS0 2 - 2-F 437 n-propyl ethyl (CH3) 2 CH(CH 2 )2θ2C-NHS0 2 - 2-F 438 n-propyl ethyl (CH 3 )2CH(CH2)2θ2C-NHSθ2- 2-F (CH 3 ) 2 CH(CH 2 )2θ 2 C-NHS0 2 - 2-F - (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F - (CH 3 )2CH(CH )2θ2C-NHSθ2- 2-F - (CH3)2CH(CH 2 )2θ2C-NHSθ2- 2-F - (CH3)2CH(CH )2θ2C-NHSθ2- 2-F - (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F - (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- 2-F - (CH3)2CH(CH2)2θ2C-NHSθ2- 2-F - (CH 3 )2CH(CH 2 )2θ2C-NHSθ2- H - (CH 3 )2CH(CH )2θ2C-NHSθ2- H - (CH3)2CH(CH2)2θ2C-NHSθ2- H - (CH3)2CH(CH2)2θ2C-NHSθ2- H - (CH3)2CH(CH2)2θ2C-NHSθ2- H - (CH3)2CH(CH2)2θ2C-NHSθ2- H - (CH3)2CH(CH )2θ2C-NHSθ2- H - 2'-(CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2- CI 2'-(CH3)2CH(CH2)2θ2C-NHS0 2 - 2-CI 2'-(CH3)2CH(CH 2 )2θ2C- NHSO2- 2-CI 2'-(CH 3 )2CH(CH 2 )2θ2C-NHSO2- 2-CI 2'-(CH3)2CH(CH2)2θ2C-NHSO2- 2-CI 2'-(CH3)2CH(CH )2θ2C-NHSO2- 2-CI 2 , -(CH 3 )2CH(CH 2 )2θ2C-NHSO2- 2-CI 2'-(CH3)2CH(CH 2 )2θ2C-NHSO2- 2-Br 2'-(CH 3 )2CH(CH2)2θ2CNHSO2- 2-Br 2'-(CH3)2CH(CH2)2θ2C-NHSO2- 2-Br 2'-(CH3)2CH(CH2)2θ2C-NHSO2- 2-Br 465 n-propyl ethyl -Cθ2(CH2)2CONHPh 2'-(CH3)2CH(CH2)2θ2C- HSθ2- 2-Br 466 n-propyl ethyl -Cθ2(CH2)3CONHPh 2'-(CH3)2CH(CH2)2θ2C-NHSθ2- 2-Br 467 n-propyl ethyl -Cθ2(CH 2 )4CONHPh 2'-(CH3) 2 CH(CH 2 )2θ2C-NHSθ2- 2-Br 468 n-propyl cyclpropyl 2'-(CH 3 )2CH(CH2)2θ2C-NHSθ2- 2-CI 5'-I 469 n-propyl CI (CH3) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F 470 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F 471 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 C2C-NHS0 2 - 2-F 472 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 C»2C-NHS0 2 - 2-F 473 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 0 2 C-NHS0 2 - 2-F 474 n-propyl CI CH3(CH 2 )3θ2C-NHSθ2- 2-F 475 n-propyl CI CH3(CH 2 )3θ 2 C-NHSθ2- 2-F 476 n-propyl CI CH 3 (CH 2 )3θ2C-NHSθ2- 2-F -CH 2 NH 477 n-propyl CI N-(CH 2 Ph) 2 CH 3 (CH 2 )3θ2C-NHS0 2 - 2-F -CH 2 NH o 478 n-propyl CI N-(Ph) 2 CH 3 (CH 2 )3θ2C-NHS0 2 - 2-F 479 n-propyl CI (CH 3 ) 2 CH(CH2)2θ2C-NHSθ2- 2-F 480 n-propyl CI (CH 3 ) 2 CH(CH2) 2 0 2 C-NHS0 2 - 2-F 481 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 θ2C-NHS0 2 - 2-F 482 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 02C-NHS0 2 - 2-F 483 n-propyl CI (CH 3 ) 2 CH(CH 2 ) 2 0 C-NHS0 2 - 2-F 484 n-propyl CI CH 3 (CH 2 )3θ2C-NHS0 2 - 2-F 485 n-propyl CI CH 3 (CH 2 ) 3 0 2 C-NHS0 2 - 2-F 486 n-propyl CI CH 3 (CH 2 ) 3 θ2C-NHS0 2 - 2-F 487 n-propyl CI CH 3 (CH 2 ) 3 0 2 C-NHS0 2 - 2-F 488 n-propyl CI CH 3 (CH 2 ) 3 0 2 C-NHS0 2 - 2-F Exampie 489 Preparation of 1-(2'-f π-amvloxycarbonvl-amino^sulfonvn-3-fluoro-(1.1 '- biphenvlV4-vnmethvn-5-t2-rN-benzovl-N-phenvlamino)ethvlcarbonvl--4-ethvl- 2-propyl-1 H-imidazole Part A: Preparation of 1 -(2-fluoro-4-bromobenzyl)-4-ethyl-2-propyl-1 H- imidazole-5-carboxaldehyde this compound was prepared following the same method described in part A of Example 3 (60% yield). 1 HNMR (300MHz, CDCI 3 ): δ 0.95 (t, 3H, CH 3 ), 1.32 (t, 3H, CH 3 ), 1.70 (m, 2H, CH 2 ), 2.60 (m, 2H, CH 2 ), 2.85 (q, 2H, CH 2 ), 5.52 (s, 2H, ArCH 2 ), 6.60 (t, 1 H, ArH), 7.18 (d, 1 H, ArH), 7.25 (d, 1 H, ArH), 9.75 (s, 1 H, CHO). Part B: Preparation of 1-(2-fluoro-4-bromobenzyl)-4-ethyl-2-propyl-1 H- imidazole-5-vinyl ketone To a solution of 1 -(2-fluoro-4-bromobenzyl)-4-ethyl-2-propyl-1 H- imidazole-5-carboxaldehyde (21.58 g, 61.1 mmol) in THF (150 mL) was added vinylmagnesium bromide (92 mL of 1.0 M solution in THF, 92.0 mmol)over 30 min. The reaction mixture was stirred at room temperature under N2 for 1 h. It was then quenched with 100 mL of 1 N aqueous HCI. The mixture was extracted with CH2CI2, the organic solution was washed with H2O and brine, dried over MgSO 4 and concentrated to an orange oil. The resulting oil was dissolved in CH2CI2 and manganese (IV) oxide (79.97 g, 920 mmol) was added. The resulting mixture was stirred at room temperature under N2 overnight. The mixture was filtered through celite and washed with CH2CI2. The CH2CI2 solution was concentrated and chromatographed on silica gel with 1/1 ethyl acetate/hexane to yield 20.4 g yellow oil. 1 HNMR (300MHz, CDCI3): δ 0.95 (t, 3H, CH 3 ), 1.30 (t, 3H, CH 3 ), 1.70 (m, 2H, CH 2 ), 2.60 (m, 2H, CH 2 ), 2.88 (q, 2H, CH ), 5.48 (s, 2H, ArCH 2 ), 5.80 (d, 1 H, CH=), 6.30 & 6.62 (d, 2H, =CH ), 6.90 (t, 1 H, ArH), 7.15 (d, 1 H, ArH), 7.25 (d, 1 H, ArH). Part C: Preparation of 1-(2-fluoro-4-bromobenzyl)-5-[2-(N- phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole To a solution of 1-(2-fluoro-4-bromobenzyl)-4-ethyl-2-propyl-1 H- imidazole-5-vinyl ketone (2.06 g, 5.41 mmol) and triethylamine (2.50 mL, 16.5 mmol) in THF (100 mL) was added aniline (1.50 mL, 16.5 mmol). The mixture was refluxed under N2 for 7 h. The solvent was removed in vacuo. The residue was dissolved in EtOAc, and washed with H2O and brine. The organic solution was then dried over MgS0 4 and concentrated, the crude mixture was chromatographed on silica gel with 30-50% EtOAc/hexane to yield 2.03 g off-white solid (83%). 1 HNMR (300MHz, CDCI3): δ 0.97 (t, 3H, CH 3 ), 1.32 (t, 3H, CH3), 1.68 (m, 2H, CH 2 ), 2.58 (t, 2H, CH 2 ), 2.90 (q, 2H, CH 2 ), 3.04 (t, 2H, CH 2 ), 3.49 (t, 2H, CH 2 ), 3.92 (s, 1 H, NH), 5.49 (s, 2H, ArCH 2 ), 6.41 (t, 1 H, ArH),6.57 (d, 2H, ArH), 6.71 (t, 1 H, ArH), 7.15 (m, 3H, ArH), 7.26 (m, 1 H, ArH). Part D: Preparation of 1-(2-fluoro-4-bromobenzyl)-5-[2-(N-benzoyl-N- phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole To a solution of 1-(2-fluoro-4-bromobenzyl)-5-[2-(N- phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole (2.16 g, 4.96 mmol) and triethylamine (1.50 mL, 10.8 mmol) in THF (100 mL) was added benzoyl chloride (1.20 mL, 10.3 mmol). The mixture was refluxed under N2 for 1 h. The solvent was removed in vacuo. The residue was dissolved in EtOAc, and washed with H2O, and then 1 N NaOH and brine. The organic solution was then dried over MgSO 4 and concentrated to a yellow oil (2.70 g, 94% yield). MS m/e 578.2,[M+H]+; 1 HNMR (300MHz, CDCI3): δ 0.95 (t, 3H, CH 3 ), 1.27 (t, 3H, CH 3 ), 1.66 (m, 2H, CH 2 ), 2.55 (t, 2H, CH 2 ), 2.90 (q, 2H, CH 2 ), 3.18 (t, 2H, CH 2 ), 4.22 (t, 2H, CH ), 5.38 (s, 2H, ArCH 2 ), 6.40 (t, 1 H, ArH),6.98 (d, 2H, ArH), 7.10-7.30 (m, 5H, ArH), 7.55 (t, 2H, ArH), 7.70 (t, 1 H, ArH), 8.15 (d, 2H, ArH). Part E: Preparation of 1-((2 , -((t-buty!amino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4- yl)methyl)-5-[2-(N-phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole 1 -(2-fluoro-4-bromobenzyl)-5-[2-(N-phenylamino)ethylcarbonyl-4-ethyl- 2-propyl-1 H-imidazole (2.20 g, 3.82 mmol), 2-(t-butylamino)sulfonylphenyl boronic acid (1.23 g, 4.78 mmol), and soduim carbonate (5 mL of 2M aqueous solution), and tetrabutylammonium bromide (60 mg, 5%) were added together with 25 mL of toluene. Tetrakis(triphenylphosphine) palladium(O) (0.22 g, 5%) was added. The mixture was refluxed under N2 for 4h. The solvent was removed in vacuo and the residue was partitioned between H2O and CH2CI2. The aqueous layer was extracted with CH 2CI2. and the combined organic solution was washed with brine, dried over MgSO 4 and concentrated. The crude product was purified by flash column chromatography ( silica gel, 50% EtOAc/hexane) to give 1.66 g of pale yellow foam (61 %). MS m/e 709.3, [M+H]+; 1H NMR ( 300 MHz, CDCI3): δ θ.95 (t, 3H, CH3), 0.99 (t, 9H, CH3). 1.30 (t, 3H, CH3), 1.70 (m, 2H, CH2), 2.60 (t, 2H, CH2), 2.90 (q, 2H, CH2), 3.22 (t, 2H, CH2), 3.57 (s, 1 H, NH), 4.22 (t, 2H, CH2), 5.50 (s, 2H, CH2Ar), 6.60 (t, 1 H, ArH), 7.02 (d, 3H, ArH), 7.10-7.30 (m, 10H, ArH), 7.50 (m, 2H_ ArH), 8.15 (d, 1 H, ArH). Part F: Preparation of 1-((2'-(aminosulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole 1-((2'-((t-butylamino)sulfonyl)-3-fluoro-(1 ,1 , -biphenyl)-4-yl)methyl)-5 - [2-(N-phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole (1.66 g, 2.34 mmol) was refluxed with 25 mL of trifluoroacetic acid under N 2 for 2.5 h. The solvent was removed in vacuo. The residue was dissolved in CH 2CI2, and washed with aqueous NaHCO 3 and brine. The organic solution was filtered through phase separator paper and then concentrated to a light yellow foam (1.39 g). MS m/e 695.2, [M+H]+; 1 H NMR ( 300 MHz, CDCI3): δ θ.98 (t, 3H, CH3), 1.27 (t, 3H, CH3). 1.72 (m, 2H, CH2), 2.68 (t, 2H, CH2), 2.88 (q, 2H, CH2), 3.12 (t, 2H, CH2), 4.20 (t, 2H, CH2), 4.40 (s, 2H, NH 2 ), 5.50 (s, 2H, CH2Ar), 6.63 (t, 1 H, ArH), 7.00 (d, 3H, ArH), 7.10-7.30 (m, 11 H, ArH), 7.50- 7.60 (dd, 2H, ArH), 8.15 (d, 1 H, ArH). Part G: Preparation of 1-((2'-((i-amyloxycarbonyl-amino)sulfonyl)-3-fluoro - (1 ,1 '-biphenyl)-4-yl)methyl)-5-[2-(N-phenylamino)ethylcarbonyl-4-ethyl-2 - propyl-1 H-imidazole 1-((2'-(aminosulfonyl)-3-fluoro-(1 ,1 , -biphenyl)-4-yl)methyl)-5-[2-(N - phenylamino)ethylcarbonyl-4-ethyl-2-propyl-1 H-imidazole (0.45 g, 0.69 mmol) was dissolved in 10 mL of CH 2CI2. To the mixture was added 4-N.N- dimethylaminopyridine (0.14 g, 1.15 mmol), pyridine (2 mL), and isoamyl chloroformate (0.50 mL of 34% in toluene, 1.13 mmol). The reaction mixture was allowed to stir at room temperature under N 2 overnight. The mixture was diluted with CH 2CI2, and then washed with 10% aqueous citric acid and brine. The organic solution was filtered through phase separator paper and concentrated. It was then chromatographed on silica gel (eluted with 6:3:1 hexane/ethyl acetate/acetone containing 0.1 % HOAc) to give 0.29 g white foam.. MS m/e 767.5, [M+H]+; 1 H NMR ( 300 MHz, CDCI3): δ 0.77 (d, 6H, CH 3 ), 0.97 (t, 3H, CH3), 1.20 (t, 3H, CH3)- 1.31 (m, 2H, CH2), 1.48 (m, 1 H, CH), 1.70 (m, 2H- CH2), 2.59 (t, 2H, CH2), 2.77 (q, 2H, CH2), 3.06 (t, 2H, CH2), 3.79 (t, 2H. CH2), 4.29 (t, 2H, CH 2 ), 5.24 (s, 2H, CH2Ar), 6.40 (t, 1 H, ArH), 6.97 (d, 3H, ArH), 7.02 (m, 2H, ArH), 7.07-7.25 (m, 9H, ArH), 7.37 (m, 2H, ArH), 8.16 (d, 1 H, ArH). Exa ple 49Q Preparation of 1-((2'-((i-amloxycarbonyl-amino sulfonvπ-3-fluoro- (1.1'- biphenyl) -4-y methyl) -5- [2-(N-nicotinoyl-N-3-pyridinoamino) ethylcarbonyl- 4-ethyl -2-propyl-1 H-imidazole The title compound was prepared by the same methods described in Example 489 from the appropriate starting materials. MS (NH 3.DCI) 769, [M+H]+; 1H NMR (300 MHz, CDC13): δ 0.86 (d, 6H, CH 3 ), 0.97 (t, 3H, CH), 1.72 (m,3H,CH 3 ), 2.52 (t, 3H, CH 3 ), 1.38 (m, 2H, CH 2 ), 1.50 (m, 1 H, CH) 1.72 (m, 2H, CH 2 ), 2.52 (t, 2H, CH 2 ), 2.98 (q, 2H, CH 2 ), 3.34 (br.s, 2H, CH 2 ), 4.00 (t, 2H, CH 2 ), 4.38 (br.s, 2H, CH 2 ), 5.40 (br.s, 2H, CH 2 AR), 6.10 (t, 1 H, ArH), 6.92 (d, 3H, ArH), 7.03-7.20 (m, 3H, ArH), 7.38 (dd, 2H, ArH), 7.48-7.61 (m, 4H, ArH), 7.78 (d, 1H, ArH), 8.28 (m, 2H, ArH), 8.33 (s, 1 H, ArH), 83.45 (d, 1 H, ArH). Example 491 Preparation of 1-(f2'- -amvloxvcarbonvl-amino sulfonvn-3-fluoro-(1.1'- biphenyl)-4-yl)methvn-5-r2-(N-butvrvl-N-3-pvridinoamino ethylcarbonyl-4- ethyl-2-propyl-1 H-imidazole The title compound was prepared by the same methods described in Example 489 from the appropriate starting materials MS (FAB) 734.6, [M+H]+; 1H NMR (300 MHz, CDC13): δ 0.77 (t, 3H, CH 3 ), 0.85 (d, 6H, CH 3 ), 0.94 (t, 3H, CH 3 ), 1.34 (t, 3H, CH 3 ), 1.38-1.60 (m, 5H, CH &CH 2 ), 2.93 (q, 2H, CH 2 ), 3.21 (br.s, 2H, CH 2 ), 4.08 (t, 4H, CH 2 ), 5.50 (br.s, 2H, CH Ar), 6.19 (t, 1 H, ArH), 7.03 (dd, 1 H, ArH), 7.09 (dd, 3H, ArH), 7.22 (dd, 1 H, ArH), 7.42 (m, 1 H, ArH), 7.53-7.68 (m,3H, ArH), 7.71 (d, 1 H, ArH), 8.31 (dd, 1 H, ArH), 8.44 (dd, 1 H, ArH). Compounds 489-696 in table 5 can be prepared by the procedure described in Examples 489-491 employing appropriately substituted starting materials. TABLE 5 W R2 R 11a R 11b R10 [M+H] + W R2 R 11a R 11b R10 [M+H]- 2-pyridine 4-pyridine i-Bu 2-pyridine 4-pyridine i-amyl 3-pyridine 3-pyridine n-Pr 3-pyridine 3-pyridine n-Bu 755 3-pyridine 3-pyridine i-Bu nPr Ph n-Bu 719 3-pyridine 4-pyridine n-Pr 3-pyridine 4-pyridine n-Bu 755 3-pyridine 4-pyridine i-Bu 3-pyridine 4-pyridine i-amyl 769 4-pyridine 3-pyridine n-Pr 4-pyridine 3-pyridine n-Bu 4-pyridine 3-pyridine i-Bu 4-pyridine 3-pyridine i-amyl 4-pyridine 4-pyridine n-Pr 4-pyridine 4-pyridine n-Bu 4-pyridine 4-pyridine i-Bu 4-pyridine 4-pyridine i-amyl Ph 3-pyridine n-Pr Ph 3-pyridine n-Bu Ph 3-pyridine i-Bu Ph 3-pyridine i-amyl Ph 4-pyridine n-Pr Ph 4-pyridine n-Bu Ph 4-pyridine i-Bu Ph 4-pyridine i-amyl 768 2-pyridine Ph n-Pr 2-pyridine Ph n-Bu 2-pyridine Ph i-Bu 2-pyridine Ph i-amyl 2-pyridine n-Pr n-Pr 2-pyridine n-Pr n-Bu 2-pyridine n-Pr i-Bu 2-pyridine n-Pr i-amyl 733 3-pyridine Ph n-Pr 3-pyridine Ph n-Bu 3-pyridine Ph i-Bu 3-pyridine Ph i-amyl 3-pyridine n-Pr n-Pr 3-pyridine n-Pr n-Bu 3-pyridine n-Pr i-Bu 3-pyridine i-Pr i-amyl 734 W R2 R 11a R 11b R10 [M+H] 4-pyridine Ph n-Pr 4-pyridine Ph n-BU 4-pyridine Ph i-BU 4-pyridine Ph i-amyl 4-pyridine n-Pr n-Pr 4-pyridine n-Pr n-Bu 4-pyridine n-Pr i-Bu 4-pyridine n-Pr 1 -amyl nPr Ph n-Pr nPr Ph i-Bu nPr Ph i-Bu nPr Ph i-amyl n-Bu Ph n-Pr n-Bu Ph n-Bu n-Bu Ph i-Bu n-Bu Ph i-amyl nPr nPr n-Pr nPr nPr n-Bu nPr nPr i-Bu nPr nPr i-amyl Ph Ph n-Pr Ph Ph n-Bu Ph Ph i-Bu Ph Ph i-amyl nPr n-Bu n-Pr nPr n-Bu n-Bu nPr n-Bu i-Bu nPr n-Bu i-amyl 2-pyridine 3-pyridine n-Pr 2-pyridine 3-pyridine n-Bu 2-pyridine 3-pyridine i-Bu 2-pyridine 3-pyridine i-amyl 2-pyridine 4-pyridine n-Pr 2-pyridine 4-pyridine n-Bu 2-pyridine 4-pyridine i-Bu 2-pyridine 4-pyridine i-amyl 3-pyridine 3-pyridine n-Pr 3-pyridine 3-pyridine n-Bu 3-pyridine 3-pyridine i-Bu 3-pyridine 3-pyridine i-amyl 751 3-pyridine 4-pyridine n-Pr 3-pyridine 4-pyridine n-Bu W R2 R 11a R 11b R10 [M+H]- 3-pyridine 4-pyridine i-Bu 3-pyridine 4-pyridine i-amyl 4-pyridine 3-pyridine n-Pr 4-pyridine 3-pyridine n-Bu 4-pyridine 3-pyridine i-Bu 4-pyridine 3-pyridine i-amyl 4-pyridine 4-pyridine n-Pr 4-pyridine 4-pyridine n-Bu 4-pyridine 4-pyridine i-Bu 4-pyridine 4-pyridine i-amyl Ph 3-pyridine n-Pr Ph 3-pyridine n-Bu Ph 3-pyridine i-Bu Ph 3-pyridine i-amyl Ph 4-pyridine n-Pr Ph 4-pyridine n-Bu Ph 4-pyridine i-Bu Ph 4-pyridine i-amyl 2-pyridine Ph n-Pr 2-pyridine Ph n-Bu 2-pyridine Ph i-Bu 2-pyridine Ph i-amyl 2-pyridine n-Pr n-Pr 2-pyridine n-Pr n-Bu 2-pyridine n-Pr i-Bu 2-pyridine n-Pr i-amyl 3-pyridine Ph n-Pr 3-pyridine Ph n-Bu 3-pyridine Ph i-Bu 3-pyridine Ph i-amyl 3-pyridine n-Pr n-Pr 3-pyridine n-Pr n-Bu 3-pyridine n-Pr i-Bu 3-pyridine n-Pr i-amyl 716 4-pyridine Ph n-Pr 4-pyridine Ph n-Bu 4-pyridine Ph i-Bu 4-pyridine Ph i-amyl 4-pyridine n-Pr n-Pr 4-pyridine n-Pr n-Bu 4-pyridine n-Pr i-Bu 4-pyridine n-Pr i-amyl W R2 R 11a R 11b R10 [M+H]- 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 3-pyridine 3-pyridine 3-pyridine 3-pyridine 3-pyridine 3-pyridine 3-pyridine 3-pyridine 4-pyridine 4-pyridine 4-pyridine 4-pyridine 4-pyridine 4-pyridine 4-pyridine 4-pyridine Ph Ph Ph Ph Ph Ph Ph Ph 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 2-pyridine 3-pyridine 3-pyridine W R2 R 11a R 11b R10 [M+H]- 720 Angiotensin II (All) produces numerous biological responses (e.g. vasoconstriction) through stimulation of its receptors on cell membranes. For the purpose of identifying compounds such as All antagonists which are capable of interacting with All receptors, a ligand-receptor binding assay was utilized. DuP 753 and PD123177 were used as standards, and to block Angiotensin II binding to the AT 1 and AT 2 sites, respectively. DuP 753 was synthesized according to the procedures described by Carini and Duncia (U. S. 5,138,069). PD123177 was prepared using the methods described by Blankely et al. (U. S. 4,812,462). AT ! site binding was determined in a rat adrenal cortical microsome preparation or in a rat liver membrane preparation. Results for AT i binding were similar in both assays. AT 2 site binding was determined using a rat adrenal medulla preparation. For the adrenal cortical microsome and adrenal medulla preparations, the method of Chiu, et al. ( Receptor, 1, 33, 1990) was employed. For the liver membrane preparation, the method of Bauer et al. (Molecular Pharmacology, 39, 579-585, 1991 ) was used, with the following changes: male Charles River CD rats were employed; the homogenation buffer consisted of a solution of Trizma base (10 mM) and buffer consisted of a solution of Trizma base (10 mM) and EDTA (5.0 mM) adjusted to pH 7.5 with 1 N HCI; the binding buffer consisted of a solution of Trizma base (50 mM) and MgCI 2 6H2O (5 mM) adjusted to pH 7.20 with 6N HCI; and the binding was assessed using a 96 well plate format at 22°C. To illustrate the adrenal cortex assay, in brief, aliquots of a freshly prepared paniculate fraction of rat adrenal cortex were incubated with 0.15 nM [ 12 5rj All and varying concentrations of potential All antagonists in a Tris buffer. After a 1 h incubation the reaction was terminated by addition of cold assay buffer. The bound and free radioactivity were rapidly separated through glass-fiber filters, and the trapped radioactivity was quantitated by gamma counting. The inhibitory concentration (IC 50) of potential All antagonists which gives 50% displacement of the total specifically bound [ 12 5|j j S presented as a measure of the affinity of such compound for the All receptor. AT- \ site binding was determined in the presence of 10 " ^ M PD123177. AT 2 site binding was determined in the presence of 10 " 6 M DuP 753. IC50 was determined by displacement of [ 12 5|] All from the receptor by the test compound. Using the assay method described above, the compounds of this invention are found to exhibit an activity of at least IC 50 <100 nanomolar at both the AT ! and AT 2 receptors, thereby demonstrating and confirming the activity of these compounds as effective ATι/AT All receptor antagonists. The potential antihvpertensive effects of the compounds of this invention may be demonstrated by administering the compounds to awake rats made hypertensive by ligation of the left renal artery (Cangiano, et al., J. Pharmacol. Exp. Ther., 208, 310, 1979). This procedure increases blood pressure by increasing renin production with consequent elevation of All levels. Compounds are administered intravenously via cannula in the jugular vein to give a cumulative dose of 10 mg/kg. Arterial blood pressure is continuously measured directly through a carotid artery cannula and recorded using a pressure transducer and a polygraph. Blood pressure levels after treatment are compared to pretreatment levels to determine the antihvpertensive effects of the compounds. Using the in vivo methodology described above, the compounds of this invention are found to exhibit an activity (intravenous) which is 10 mg/kg or less, and/or an activity (oral) which is 100 mg/kg or less, thereby demonstrating and confirming the utility of these compounds as effective agents in lowering blood pressure. The compounds of this invention are useful in treating hypertension, and for the treatment of hyperuricemia, primary and secondary hyperaldosteronism, psoriasis, cardiac disorders such as acute and chronic congestive heart failure, angina pectoris, myocardial infarction, systolic and diastolic dysfunction, cardiac myopathy, and cardiac hypertrophy and hyperplasia, esp. left ventricular hypertrophy; pulmonary disorders such as primary and secondary pulmonary hypertension; vascular disorders such as atherosclerosis, restenosis after vascular injury associated with e.g. angioplasty or bypass surgery, vascular hypertrophy and hyperplasia, atheroma and Raynaud's disease; cerebrovascular disorders such as migraine, and ischemic and hemorragic stroke; renal disorders such as renal vascular hypertension, proteinuria of primary renal disease, end stage renal disease and renal transplant therapy, glomerulonephrife, nephrotic syndrome, scleroderma and glomerular sclerosis, and for enhancing renal blood flow; CNS disorders such as impairment of cognitive function and memory loss, addiction, anxiety, bulimia, depression, epilepsy, pain, Parkinson's disease, psychosis, sleep disorders and tardive dyskinesia; ocular disorders such as macular degeneration and elevated intraocular pressure; gastrointestinal and bladder disorders; disorders associated with diabetes, such as diabetic angiopathy, neptøopa ' and retinopathy, and for delaying the onset of type II diabetes. The application oϊ the compounds of this invention for these and similar disorders will be apparent to those skilled in the art. The compounds of this invention are also useful as diagnostic agents, to test the renin angiotensin system. Patients in need of treatment for elevated intraocular pressure can be treated with compounds of this invention administered in the form of typical pharmaceutical formulations such as tablets, capsules, injectables and the like as well as topical ocular formulations in the form of solutions, ointments, inserts, gels and the like. Pharmaceutical formulations prepared to treat intraocular pressure would typically contain about 0.1% to 15% by weight, preferably 0.5% to 2% by weight, of a compound of this invention. For this use, the compounds of this invention may also be used in combination with other medications for the treatment of glaucoma including choline esterase inhibitors such as physostigmine salicylate or demecarium bromide, parasympathomimetic agents such as pilocarpine nitrate, beta-adrenergic antagonists such as timolol maleate, adrenergic agonists such as epinephrine and carbonic anhydrase inhibitors such as MK-507. In the management of hypertension and the clinical conditions noted above, the compounds of this invention may be utilized with a pharmaceutical carrier in compositions such as tablets, capsules or elixirs for oral administration, suppositories for rectal administration, sterile solutions or suspensions for parenteral or intramuscular administration, and the like. The compounds of this invention can be administered to patients (animals and human) in need of such treatment in dosages that will provide optimal pharmaceutical efficacy. Although the dose will vary from patient to patient depending upon the nature and severity of disease, the patient's weight, special diets being followed by a patient, concurrent medication, and other factors which those skilled in the art will recognize, the dosage range will generally be about 1 to 1000 mg per patient per day which can be administered in single or multiple doses. Preferably, the dosage range will be about 5 to 500 mg per patient per day; more preferably about 5 to 300 mg per patient per day. Administration of a compound of this invention with a NSAID can prevent renal failure which sometimes results from administration of a NSAID. The compounds of this invention can also be administered in combination with other antihypertensives and/or diuretics. Administration of a compound of this invention with a diuretic, either as a stepwise combined therapy (diuretic first) or as a physical mixture, enhances the antihvpertensive effect of the compound. For example, the compounds of this invention can be given in combination with diuretics such as hydrochlorothiazide, chlorothiazide, combination with diuretics such as hydrochlorothiazide, chlorothiazide, chlorthalidone, methylclothiazide, furosemide, ethacrynic acid, triamterene, amiloride spironolactone and atriopeptin; calcium channel blockers, such as diltiazem, felodipine, nifedipine, amLodipine, nimodipine, isradipine, nitrendipine and verapamil; b-adrenergic antagonists such as timolol, atenolol, metoprolol, propanolol, nadolol and pindolol; angiotensin converting enzyme inhibitors such as enalapril, lisinopril, captopril, ramipril, quinapril and zofenopril; renin inhibitors such as A-69729, FK 906 and FK 744; a - adrenergic antagonists such as prazosin, doxazosin, and terazosin; sympatholytic agents such as methyldopa, clonidine and guanabenz; atriopeptidase inhibitors (alone or with ANP) such as UK-79300; serotonin antagonists such as ketanserin; A 2-adrenosine receptor agonists such as CGS 22492C; potassium channel agonists such as pinacidil and cromakalim; and various other antihvpertensive drugs including reserpine, minoxidil, guanethidine, hydralazine hydrochloride and sodium nitroprusside as well as combinations of the above-named drugs. Combinations useful in the management of congestive heart failure include, in addition, compounds of this invention with cardiac stimulants such as dobutamine and xamoterol and phosphodiesterase inhibitors including amrinone and milrinone.

Claims: WHAT IS CLAIMED IS: 1. A compound of Formula (I) (u) -SO2NHCOR 10 , (v) -S02NHCONHR9, H , (y) N-N 4 - -CF 3 H (CC) (dd) (ii) -SO2NHCO2R 10 ; independently (a) H, (b) -NO2, or (c) -C0 2 R 1 1 ; R5 is (a) H. (b) Cι-C6-alkyl, (c) C3-C6-cycloalkyl, (d) C2-C4-alkenyl, or (e) C2-C4-alkynyl; R6 is (a) Cι -Cιo-alkyl, (b) C3-Cιo-alkenyl, (c) C3-Cιo-alkynyl, (d) C3-C8-cycloalkyl, (e) C3-C8-cycloalkenyl, (f) -Cι-C3-alkyl-(C3-C8-cycloalkyl), (g) -Ci -C3-alkenyl-(C 5-C1 o-cycloalkyl), (h) -Cι-C3-alkynyl-(C5-Cιo-cycloalkyl), (i) -(CH2)sS(CH 2 )mR 5 , or (j) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, C 1 -C4-alkyl, Ci • C4-alkoxy or -NO2; R7 is (a) Cι -C6-alkyl, (b) C3-C6-cycloalkyl, (c) aryl, where aryl is defined above, or (d) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, C 1 -C4-alkyl, Ci • C4-alkoxy or -N02; Rδ is (a) H, (b) halogen (F.CI, Br, I), (c) phenyl or phenyl optionally substituted with halogen (F, CI, Br, I), Cι-C4-alkyl, -OH, Cι-C4-alkoxy, -N0 2 , -NR26R27 ( -NR26C0R 1 , -NR26C0 2 R 7 , -S(0) r R 10 , -Sθ2NR26R27 ι -NR26SC^R10 > -CF3, (c) Cι-C4-perfluoroalkyl, (d) Ci -C4-alkyl, optionally substituted with a substituent selected from the group consisting of aryl, heteroaryl, -OH, -SH, C ι-C4-alkyl, d- C4-alkoxy, Cι-C4-alkylthio, -CF3, halo, -NO2, -C02R 12 , -NH2, C1-C4- alkylamino, C 1 -C4-dialkylamino, -PO3H2, or (e) heteroaryl; R 1 , R11 a anc j R11 b are independently (b) Cι-C6-alkyl, (c) CH2CH=CH2, or (d) benzyl, optionally substituted on the phenyl ring with 1 -2 substituents selected from the group consisting of halo, C 1 -C4-alkyl, d C4-alkoxy or -Nθ2; Rl5 js (a) H, (b) Ci-Cβ-alkyI, (c) Ci-Cβ-perfluoroalkyI, (d) C3-C6-cycloalkyl, (e) aryl, (f) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, C ι-C4-alkyl, Ci - C4-alkoxy or -NO2; Rl6 js (a) H, (b) Cι-C6-alkyl, or (c) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, C 1 -C4-alkyl, Ci • C4-alkoxy or -NO2; Rl7 is (a) H, (b) Cι-C6-alkyl, (c) C3-C6-cycloalkyl, (d) aryl, (e) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, C 1 -C4-alkyl, Ci ■ C4-alkoxy or -N02; Rl8 js (a) -NR19R20, (b) -NHCONH2, (c) -NHCSNH 2, or (d) -NHSO2-C6H5; R19 and R20 are independently (a) H, (b) Cι-C5-alkyl, or (c) aryl, R21 and R22 are independently (a) Ci -C4-alkyl, or taken together are (b) -(CH 2 )q-; R 3 and R 2 4 are, independently (a) -CHO, (b) -CONH2, (c) -NHCHO, (d) -CO-(Cι -C6 perfluoroalkyl), (e) -S(0)r(Cι-C6 perfluoroalkyl), (f) -0-(Cι -C6 perfluoroalkyl), or (g) -NR 1 1 a-(Cι-C6 perfluoroalkyl); R 3 ° is (a) -CHO, (b) -Sθ2-(Cι-C6 perfluoroalkyl), or (c) -CO-(Cι-C6 perfluoroalkyl); A is (a) -(CH 2 )n Ll -B-(T)y-(B)y-X2-(B)y-R28, (b) -(CH 2 )n - " L '-B-T-(B)y-R28 ι (c) -(CH2)n -B-(T)y-(B)y-X2-B, (d) -(CH2)n -B-T-(B)y-R29, (e) -(CH 2 )n -T-(B)y-X2-(B)y-R28, (f) -(CH )n -T-(B)y-R28, (g) -(CH 2 )n -T-(B)y-X2-B, (h) ■ (CH )n -(CR 1 9R20). D .( T ) y -(B)y-χ3-(B)y-R28 ) 0) -(CH2)n -(CR 1 9R20). D . T .(B)y-R28 ι (j) -(CH2)n -(CR19R20). D .( T ) y .(B) y -χ3-B, (k) -(CH )n -(CR * l9R20). D . T .(B) y .R29 i (I) -(CH 2 )n -(CR 1 9 R20)-D-T-(B) y -X4-(B)y-R28 , (m) -(CH )n -(CR 1 9R20). D . B -χ4.(B) y -R28 f (n) -(CH2)n -(CR 1 9R20). D . T .( B )y-χ4. B) (o) -(CH 2 )n _ -(CR19R20).D-B-X4.B, (P) -(CH )n . L 2. B -(T)y-(B)y-X2-(B)y-R28 > (q) -(CH )n ■L2-B-T-(B)y-R28, (r) -(CH 2 )n •L2-B-(T)y-(B) y -χ2-B, (s) -(CH 2 )n ■L2-B-T-(B) y -R29 ι (t) -(CH )n ■L2-T-(B)y-χ2-(B) y -R28 ) -(CH2)n- 2-T-(B) y -R28, -(CH2)n-L 2 -T-(B)y-X2-B. -(CH2)n- 2-D-(T)y-(B)y-X3-(B)y-R28, -(CH2)n- 2-D-T-(B) y -R28, -(CH2)n- 2-D-(T)y-(B)y-X3-B, -(CH2)n- 2-D-T-(B)y-R29, -(CH2)n-L 2 -D-T-(B)y-X4-(B)y-R28, -(CH2)n-L 2 -D-B-χ4.(B)y-R28, -(CH2)n- 2 -D-T-(B)y-X4-B, -(CH2)n- 2 -D-B-χ4-B, -(CH2)m- 3-B-(T)y-(B)y-X2-(B)y-R28, -(CH2)m-L3-B-T-(B) y -R28, -(CH 2 )m- 3-B-(T)y-(B)y-X2-B, -(CH 2 )m-L3-B-T-(B) y -R29, -(CH2)m-L3-T-(B)y-χ2-(B) y -R28 ) -(CH2)m-L3-T-(B) y -R28, -(CH 2 )m-L3-T-(B) y -χ2-B, -(CH2)m-L 3 -(CRl 9R20). D .(T) y .(B)y-χ3-(B) y -R28 ι -(CH2)m-L3-(CRl9R20).D-T-(B)y-R28, -(CH2)m- 3 -(CRl9R20). D -(T)y-(B)y-χ3-B, (CH2)m-L 3 -(CR 1 9R20)-D-T-(B)y-R29, -(CH2)m-L3-(CRl9R20).D-T-(B)y-X4-(B) y -R28, -(CH2)m-L 3 -(CRl9R20).D-(B)-X4-(B)y-R28, -(CH2)m-L 3 -(CRl9R20). D . T .( B )y-χ4-B, -(CH2)m-L 3 -(CRl 9R20)_D-B-X4-B, (tt) (w) (ww) »30 (xx) X 5 -(B) y -R (yy) R 30 -(CH 2 ) n -L 1 -(CR 19 R 20 )-D— - {( I ) (22) (aaa) R 30 (bbb) X^(B) y -R 28 (ccc) R 30 -(CH 2 ) m -L 3 .(CR u is 2 to 5; y is 0 or 1 ; wherein aryl is phenyl, biphenyl, napthyl, or fluorenyl group optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, Cι-C4-alkyl, Cι-C4-alkoxy, -CF3, halo, -NO2, -CO2H- -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι-C4-alkyl), -N(Cι-C4-alkyl)2.; wherein heteroaryl is 2-, 3-, or 4-pyridyl; 2-, or 3-furyl; 2-, or 3-thiophenyl; 2-, 3-, or 4-quinolinyl; or 1 -, 3-, or 4-isoquinolinyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, C 1-C4- alkyl, Cι-C4-alkoxy, -CF3- halo, -NO2, -CO2H, -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι-C4-alkyl), -N(Cι -C4-alkyl)2; wherein arylene is 1,2-phenyl, 1 ,3-phenyl, 1 ,4-phenyl, 4,4'-biphenyl, 3,3' - biphenyl, and 2,2'-biphenyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, C ι -C4-alkyl, C1- C4-alkoxy, -CF3, halo, -NO2, -CO2H, -C02CH3, -Cθ2-benzyl, -NH2, -NH(Ci-C4-alkyl), -N(Cι-C4-alkyl)2.; and wherein heteroarylene is 2,3-pyridyl, 3,4-pyridyl, 2,3-furyl, 3,4-furyl, 2,3 - thiophenyl, 3,4-thiophenyl, 2,3-quinolinyl, 3,4-quinolinyl and 1 ,4 - isoquinolinyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, C ι-C4-alkyl, Cι-C4-alkoxy, -CF3, halo, -NO2, -CO2H, -C02CH3, -Cθ2-benzyl, -NH2, -NH(Cι -C4-alkyl), -N(Cι - C4-alkyl)2; and pharmaceutically acceptable salts of these compounds. 2. A compound of claim 1 wherein R 1 is R13 and pharmaceutically acceptable salts of these compounds. 3. A compound of formula (b) C3-C7-cycloalkyl, (c) Cι -C4-perfluoroalkyl, (d) Ci -C4-alkyl, optionally substituted with a substituent selected from the group consisting of aryl heteroaryl, -OH, -SH, C 1 -C4-alkyl, Ci - C4-alkoxy, Cι-C4-alkylthio, -CF3, halo, -NO2, -CC^R 12 , -NH2, C1-C4- alkylamino, C 1 -C4-dialkylamino, -PO3H2, or (e) heteroaryl; R11 1 R11 a anc j R11 b a re independently (c) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group consisting of halo, C ι-C4-alkyl, C C4-alkoxy or -NO2; R 28 is (j) -CONRHasθ2-, (k) -Sθ2NRHacθ-, (I) -Sθ2NRH cθ2-, (m) -OCONRl 1asθ2-, (n) -Sθ2NR"l 1acθNRl 1b. ι (0) -NR 11 acθNRHbsθ2-, (p) -Sθ2NRHasθ2-, (q) -CONR11 sθ2NRl 1 b-, or (r) -NR 11 as02NR " lbC0-; wherein aryl is phenyl, biphenyl, napthyl, or fluorenyl group optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, Cι-C4-alkyl, Cι-C4-alkoxy, -CF3, halo, -NO2, -CO2H, -CO2CH3. -Cθ2-benzyl, -NH2, -NH(Cι -C4-alkyl), -N(Cι -C4-alkyl)2; wherein heteroaryl is 2-, 3-, or 4-pyridyl; 2-, or 3-furyl; 2-, or 3-thiophenyl; 2-, 3-, or 4-quinolinyl; or 1-, 3-, or 4-isoquinolinyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, C 1 -C4- alkyl, Cι-C4-alkoxy, -CF3- halo, -NO2, -CO2H, -CO2CH3- -Cθ2-benzyl, -NH2, -NH(Cι-C4-alkyl), -N(Cι-C4-alkyl)2; and pharmaceutically acceptable salts of these compounds. 4. A compound of formula III (b) C3-C7-cycloalkyl, (c) Cι -C4-perfluoroalkyl, (d) Ci -C4-alkyl, optionally substituted with a substituent selected from the group consisting of aryl, heteroaryl, -OH, -SH, C 1 -C4-alkyl, d C4-alkoxy, Cι-C4-alkylthio, -CF3, halo, -NO2, -CC^R 12 , -NH2, C1-C4- alkylamino, C 1 -C4-dialkylamino, -PO3H2, or (e) heteroaryl; R11 ( R11 a and R 11 b are independently (b) Cι-C6-alkyl, or (c) benzyl, optionally substituted on the phenyl ring with 1 -2 substituents selected from the group consisting of halo, C ι-C4-alkyl, Ci- C4-alkoxyor-Nθ2; R28is (I) -Sθ2NRHacθ2-, (m) -OCONR 1 1 asθ2-, (n) -Sθ2NRl 1 cθNR * H b. t (o) -NR 1acθNR 1 bsθ2-, (p) -Sθ2NRHasθ2-, (q) -CONR11 asθ2NRl 1 b-, or (r) -NRl 1 sθ2NRl 1 bcθ-; wherein aryl is phenyl, biphenyl, napthyl, or fluorenyl group optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, Cι -C4-alkyl, Cι -C4-alkoxy, -CF3, halo, -NO2, -CO2H, -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι -C4-alkyl), -N(Cι -C4-alkyl)2; wherein heteroaryl is 2-, 3-, or 4-pyridyl; 2-, or 3-furyl; 2-, or 3-thiophenyl; 2-, 3-, or 4-quinolinyl; or 1-, 3-, or 4-isoquinolinyl optionally substituted with one to three substituents selected from the group consisting of -OH, -SH, C 1-C4- alkyl, Cι -C4-alkoxy, -CF3, halo, -NO2, -CO2H, -CO2CH3, -Cθ2-benzyl, -NH2, -NH(Cι -C4-alkyl), -N(Cι -C4-alkyl)2; and pharmaceutically acceptable salts of these compounds. 5. A compound of claim 3 selected from the group consisting of: 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl] 3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1 - yl)methyl]-3-fluoro-2'-((2-phenyl)ethyloxycarbonylaminosulfonyl)-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl] 2'-((2-phenyl)ethyloxycarbonylaminosulfonyl)-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1-yl)methyl] 3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1 -yl)methyl] 3-fluoro-2'-n-isoamyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1 -yl)methyl] 2'-n-isoamyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1 - yl)methyl]-3-fluoro-2'-n-propyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-lsoamyloxybenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1 - yl)methyl]-3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl 4-[((5-(2-Phenylaminocarbonyl)benzyloxycarbonyl-4-ethyl-2-n - propyl)imidazol-1-yl)methyl]-3-fluoro-2'-n-butyloxycarbonylaminosulfonyl-1 ,1' biphenyl. 4-[((5-(2-Benzoylbenzyloxycarbonyl)-4-ethyl-2-n-propyl)imidazol-1 yl)methyl]-3-fluoro-2'-(1 H-tetrazol-5-yl)-1 ,1 '-biphenyl 4-[((5-)2-trifluorophenyl)methylaminocarbonyl)-4-ethyl-2-n-propyl)imidazol-1 yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonyl-1 ,1 '-biphenyl N-butyl, N-benzyl-2-(aminocarbonyl)ethynylmethyl 4-ethyl-2-propyl-1-[[2'-(1 H tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N, N-diphenyl-2-(aminocarbonyl)ethynylmethyl 4-ethyl-2-propyl-1-[[2'-(1 H - tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N-phenyl-2-(aminocarbonyl)ethyl 4-ethyl-2-propyl-1 -[[2'-(1 H-tetrazol-5 - yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N-butyl, N-benzyl-4-(aminocarbonyl)propyl 4-ethyl-2-propyl-1 -[[2'-(1 H-tetrazol 5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate N, N-dipentyl-4-(aminocarbonyl)propyl 4-ethyl-2-propyl-1-[[2'-(tetrazol-5 - yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate 6. A compound of claim 4 selected from the group consisting of: 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-benzoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H imidazole ■ 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-benzoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl - 1 H-imidazole 1-((2'-((n-Propyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4 - yl)methyl)-5-[2-(N-benzoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-benzoyl-N-butylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1,1 '-biphenyl)-4 - yl)methyl)-5-[2-(N-benzoyl-N-propylamino)ethylcarbonyI]-4-ethyl-2-propyl-1 H imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4 - yl)methyl)-5-[2-(N-butyryl-N-propylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1 -((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 * -biphenyl)-4 - yl)methyl)-5-[2-(N-butyryl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl - 1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl) 5-[2-(N-butyryl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl) 5-[2-(N-isonicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-isonicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2 - propyl-1 H-imidazole 1-((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-nicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2 - propyl-1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl) 5-[2-(N-nicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1 -((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4 - yl)methyl)-5-[2-(N-nicotinoyl-N-pyridin-2-ylamino)ethylcarbonyl]-4-ethyl-2 - propyl-1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl) 5-[2-(N-isonicotinoyl-N-phenylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-5-[2-(N-butyryl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl 1 H-imidazole 1 -((2'-((i-Amyloxyrarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4-yl)methyl) 5-[2-(N-isobutyryl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1 -((2'-((n-Butyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4 - yl)methyl)-5-[2-(N-acetyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl - 1 H-imidazole 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4-yl)methyl) 5-[2-(N-butyryl-N-pyridin-2-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1 -((2'-((i-Amyloxycarbonylamino)sulfonyl)-(1 ,1 '-biphenyl)-4-yl)methyl)-5-[2-(N butyryl-N-pyridin-3-ylamino)ethylcarbonyl]-2-butyl-4-chloro-1 H-imidazole 1 -((2'-((i-amyloxycarbonylamino)sulfonyl)-3-fluoro-(1 ,1 '-biphenyl)-4-yl)methyl) 5-[2-(N-propionyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H - imidazole 1 -((2'-((i-Amyloxycarbonylamino)sulfonyl)(1 ,1 '-biphenyl)-4-yl)methyl)-5-[2 - (N-nicotinoyl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H-imidazole 1 -((^-((i-AmyloxycarbonylaminoJsulfony^l , 1 '-biphenyl)-4-yl)methyl)-5-[2-(N - butyryl-N-pyridin-3-ylamino)ethylcarbonyl]-4-ethyl-2-propyl-1 H-imidazole 1-((2 * -((n-Butyloxycarbonyl-amino)sulfonyl)-3-fluoro-(1 ,1'-biphenyl)-4 - yl)methyl)-4-ethyl-5-(2-(2-phenoxyphenyl)ethylcarbonyl)-2-propyl-1H - imidazole 4-[(5-((2-benzoyl)phenylcarbonyloxymethyl)-4-chloro-2-n-propylimidazol-1 - yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonylbiphenyl 1-((2'-((n-butyloxycarbonylamino)sulfonyl)-3-fluoro-(1,1'-biphenyl)-4 - yl)methyl)-2-(n-propyl)-4-ethyl-5-(2-(phenoxy)phenoxy)acetyl-1 H-imidazole 7. A pharmaceutical composition comprising a pharmaceutically suitable carrier and a compound of any one of claims 1 through 6. 8. A method of treating hypertension in a warm blooded animal comprising administering to said animal in need of such treatment an effective amount of a compound of any of claims 1 through 6. 9. A method of treating congestive heart failure in a warn blooded animal comprising administering to said animal in need of such treatment an effective amount of a compound of any of claims 1 through 6.

Inventors: DUNCIA JOHN JONAS VYTAUTAS, ENSINGER CAROL LEE, OLSON RICHARD ERIC, QUAN MIMI LIFEN, SANTELLA JOSEPH BASIL III, VANATTEN MARY KATHERINE, DUNCIA, JOHN, JONAS, VYTAUTAS, ENSINGER, CAROL, LEE, OLSON, RICHARD, ERIC, QUAN, MIMI, LIFEN, SANTELLA, JOSEPH, BASIL, III, VANATTEN, MARY, KATHERINE
Applicants: DU PONT MERCK PHARMA, THE DU PONT MERCK PHARMACEUTICAL COMPANY
Application year: 1994
Main classification: A61K31
IPC codes: A61K31, A61P9, C07C17, C07D233, C07D401, C07D403, C07D409